Protein-Protein Interactions and Aggregation Inhibitors in Alzheimer’s Disease

Author(s): Ankit Ganeshpurkar , Rayala Swetha , Devendra Kumar , Gore P. Gangaram , Ravi Singh , Gopichand Gutti , Srabanti Jana , Dileep Kumar , Ashok Kumar , Sushil K. Singh* .

Journal Name: Current Topics in Medicinal Chemistry

Volume 19 , Issue 7 , 2019

Become EABM
Become Reviewer

Graphical Abstract:


Abstract:

Background: Alzheimer’s Disease (AD), a multifaceted disorder, involves complex pathophysiology and plethora of protein-protein interactions. Thus such interactions can be exploited to develop anti-AD drugs.

Objective: The interaction of dynamin-related protein 1, cellular prion protein, phosphoprotein phosphatase 2A and Mint 2 with amyloid β, etc., studied recently, may have critical role in progression of the disease. Our objective has been to review such studies and their implications in design and development of drugs against the Alzheimer’s disease.

Methods: Such studies have been reviewed and critically assessed.

Results: Review has led to show how such studies are useful to develop anti-AD drugs.

Conclusion: There are several PPIs which are current topics of research including Drp1, Aβ interactions with various targets including PrPC, Fyn kinase, NMDAR and mGluR5 and interaction of Mint2 with PDZ domain, etc., and thus have potential role in neurodegeneration and AD. Finally, the multi-targeted approach in AD may be fruitful and opens a new vista for identification and targeting of PPIs in various cellular pathways to find a cure for the disease.

Keywords: Alzheimer's disease, Protein-protein interactions, Amyloid beta, Tau, BACE1, Mint2, Peptidomimetics, Small molecule inhibitors.

[1]
Phizicky, E.M.; Fields, S. Protein-protein interactions: methods for detection and analysis. Microbiol. Rev., 1995, 59(1), 94-123. [PMID: 7708014].
[2]
Moreira, I.S.; Fernandes, P.A.; Ramos, M.J. Hot spots--A review of the protein-protein interface determinant amino-acid residues. Proteins, 2007, 68(4), 803-812. [http://dx.doi.org/ 10.1002/prot.21396]. [PMID: 17546660].
[3]
Rual, J.F.; Venkatesan, K.; Hao, T.; Hirozane-Kishikawa, T.; Dricot, A.; Li, N.; Berriz, G.F.; Gibbons, F.D.; Dreze, M.; Ayivi-Guedehoussou, N.; Klitgord, N.; Simon, C.; Boxem, M.; Milstein, S.; Rosenberg, J.; Goldberg, D.S.; Zhang, L.V.; Wong, S.L.; Franklin, G.; Li, S.; Albala, J.S.; Lim, J.; Fraughton, C.; Llamosas, E.; Cevik, S.; Bex, C.; Lamesch, P.; Sikorski, R.S.; Vandenhaute, J.; Zoghbi, H.Y.; Smolyar, A.; Bosak, S.; Sequerra, R.; Doucette-Stamm, L.; Cusick, M.E.; Hill, D.E.; Roth, F.P.; Vidal, M. Towards a proteome-scale map of the human protein-protein interaction network. Nature, 2005, 437(7062), 1173-1178. [http://dx.doi.org/ 10.1038/nature04209]. [PMID: 16189514].
[4]
Fletcher, S.; Hamilton, A.D. Protein-protein interaction inhibitors: Small molecules from screening techniques. Curr. Top. Med. Chem., 2007, 7(10), 922-927. [http://dx.doi.org/ 10.2174/ 156802607780906735]. [PMID: 17508923].
[5]
Fletcher, S.; Hamilton, A.D. Targeting protein-protein interactions by rational design: Mimicry of protein surfaces. J. R. Soc. Interface, 2006, 3(7), 215-233. [http://dx.doi.org/ 10.1098/rsif.2006. 0115]. [PMID: 16849232].
[6]
Uetz, P.; Giot, L.; Cagney, G.; Mansfield, T.A.; Judson, R.S.; Knight, J.R.; Lockshon, D.; Narayan, V.; Srinivasan, M.; Pochart, P.; Qureshi-Emili, A.; Li, Y.; Godwin, B.; Conover, D.; Kalbfleisch, T.; Vijayadamodar, G.; Yang, M.; Johnston, M.; Fields, S.; Rothberg, J.M. A comprehensive analysis of protein-protein interactions in Saccharomyces cerevisiae. Nature, 2000, 403(6770), 623-627. [http://dx.doi.org/ 10.1038/35001009]. [PMID: 10688190].
[7]
Modell, A.E.; Blosser, S.L.; Arora, P.S. Systematic targeting of protein–protein interactions. Trends Pharmacol. Sci., 2016, 37(8), 702-713. [http://dx.doi.org/ 10.1016/j.tips.2016.05.008]. [PMID: 27267699].
[8]
Thompson, A.D.; Dugan, A.; Gestwicki, J.E.; Mapp, A.K. Fine-tuning multiprotein complexes using small molecules. ACS Chem. Biol., 2012, 7(8), 1311-1320. [http://dx.doi.org/ 10.1021/ cb300255p]. [PMID: 22725693].
[9]
Stevers, L.M.; Sijbesma, E.; Botta, M.; MacKintosh, C.; Obsil, T.; Landrieu, I.; Cau, Y.; Wilson, A.J.; Karawajczyk, A.; Eickhoff, J.; Davis, J.; Hann, M.; O’Mahony, G.; Doveston, R.G.; Brunsveld, L.; Ottmann, C. Modulators of 14-3-3 protein–protein interactions. J. Med. Chem., 2018, 61(9), 3755-3778. [http://dx.doi.org/ 10.1021/acs.jmedchem.7b00574]. [PMID: 28968506].
[10]
Park, A. Characterization of a novel class of anti-HCV agents targeting protein-protein interactions, Ph.D. Thesis, Universite de Montreal, September.. 2017.
[11]
Zinzalla, G.; Thurston, D.E. Targeting protein-protein interactions for therapeutic intervention: A challenge for the future. Future Med. Chem., 2009, 1(1), 65-93. [http://dx.doi.org/ 10.4155/ fmc.09.12]. [PMID: 21426071].
[12]
Mannhold, R.; Kubinyi, H.; Folkers, G. Protein-protein interactions in drug discovery; Wiley & Sons: New York, 2013, Vol. 56, .
[13]
Srinivasa Rao, V.; Srinivas, K.; Kumar, G.N.S.; Sujin, G.N. Protein interaction network for Alzheimer’s disease using computational approach. Bioinformation, 2013, 9(19), 968-972. [http://dx.doi.org/ 10.6026/97320630009968]. [PMID: 24391359].
[14]
Malhotra, A.; Younesi, E.; Sahadevan, S.; Zimmermann, J.; Hofmann-Apitius, M. Exploring novel mechanistic insights in Alzheimer’s disease by assessing reliability of protein interactions. Sci. Rep., 2015, 5, 13634-13634. [http://dx.doi.org/ 10.1038/srep13634]. [PMID: 26346705].
[15]
Karbalaei, R.; Allahyari, M.; Rezaei-Tavirani, M.; Asadzadeh-Aghdaei, H.; Zali, M.R. Protein-protein interaction analysis of Alzheimer’s disease and NAFLD based on systems biology methods unhide common ancestor pathways. Gastroenterol. Hepatol. Bed Bench, 2018, 11(1), 27-33. [PMID: 29564062].
[16]
Mehta, D.; Jackson, R.; Paul, G.; Shi, J.; Sabbagh, M. Why do trials for Alzheimer’s disease drugs keep failing? A discontinued drug perspective for 2010-2015. Expert Opin. Investig. Drugs, 2017, 26(6), 735-739. [http://dx.doi.org/ 10.1080/13543784.2017. 1323868]. [PMID: 28460541].
[17]
Rygiel, K. Novel strategies for Alzheimer’s disease treatment: An overview of anti-amyloid beta monoclonal antibodies. Indian J. Pharmacol., 2016, 48(6), 629-636. [http://dx.doi.org/ 10.4103/ 0253-7613.194867]. [PMID: 28066098].
[18]
Cummings, J.; Lee, G.; Ritter, A.; Zhong, K. Alzheimer’s disease drug development pipeline: 2018. Alzheimers Dement. (N. Y.), 2018, 4, 195-214. [http://dx.doi.org/ 10.1016/j.trci.2018.03.009]. [PMID: 29955663].
[19]
Laraia, L.; McKenzie, G.; Spring, D.R.; Venkitaraman, A.R.; Huggins, D.J. Overcoming chemical, biological, and computational challenges in the development of inhibitors targeting protein-protein interactions. Chem. Biol., 2015, 22(6), 689-703. [http://dx.doi.org/ 10.1016/j.chembiol.2015.04.019]. [PMID: 26091166].
[20]
Valkov, E.; Sharpe, T.; Marsh, M.; Greive, S.; Hyvönen, M. Targeting protein–protein interactions and fragment-based drug discovery. Top. Curr. Chem., 2011, 317, 145-179. [http://dx.doi.org/ 10.1007/128_2011_265].
[21]
Azzarito, V.; Long, K.; Murphy, N.S.; Wilson, A.J. Inhibition of α-helix-mediated protein-protein interactions using designed molecules. Nat. Chem., 2013, 5(3), 161-173. [http://dx.doi.org/ 10.1038/nchem.1568]. [PMID: 23422557].
[22]
Watkins, A.M. An in silico pipeline for the design of peptidomimetic protein-protein interaction inhibitors; ProQuest LLC, 2016.
[23]
Gul, S.; Hadian, K. Protein-protein interaction modulator drug discovery: Past efforts and future opportunities using a rich source of low- and high-throughput screening assays. Expert Opin. Drug Discov., 2014, 9(12), 1393-1404. [http://dx.doi.org/ 10.1517/ 17460441.2014.954544]. [PMID: 25374163].
[24]
Driggers, E.M.; Hale, S.P.; Lee, J.; Terrett, N.K. The exploration of macrocycles for drug discovery-An underexploited structural class. Nat. Rev. Drug Discov., 2008, 7(7), 608-624. [http://dx.doi.org/ 10.1038/nrd2590]. [PMID: 18591981].
[25]
Meireles, L.M.; Mustata, G. Discovery of modulators of protein-protein interactions: Current approaches and limitations. Curr. Top. Med. Chem., 2011, 11(3), 248-257. [http://dx.doi.org/ 10.2174/ 156802611794072632]. [PMID: 21320056].
[26]
González-Ruiz, D.; Gohlke, H. Targeting protein-protein interactions with small molecules: Challenges and perspectives for computational binding epitope detection and ligand finding. Curr. Med. Chem., 2006, 13(22), 2607-2625. [http://dx.doi.org/ 10.2174/ 092986706778201530]. [PMID: 17017914].
[27]
Kuret, J.; Congdon, E.E.; Li, G.; Yin, H.; Yu, X.; Zhong, Q. Evaluating triggers and enhancers of tau fibrillization. Microsc. Res. Tech., 2005, 67(3-4), 141-155. [http://dx.doi.org/ 10.1002/ jemt.20187]. [PMID: 16103995].
[28]
Scott, D.E.; Bayly, A.R.; Abell, C.; Skidmore, J. Small molecules, big targets: drug discovery faces the protein-protein interaction challenge. Nat. Rev. Drug Discov., 2016, 15(8), 533-550. [http://dx.doi.org/ 10.1038/nrd.2016.29]. [PMID: 27050677].
[29]
Whitebread, S.; Hamon, J.; Bojanic, D.; Urban, L. Keynote review: In vitro safety pharmacology profiling: An essential tool for successful drug development. Drug Discov. Today, 2005, 10(21), 1421-1433. [http://dx.doi.org/ 10.1016/S1359-6446(05)03632-9]. [PMID: 16243262].
[30]
Fry, D.C.; Vassilev, L.T. Targeting protein-protein interactions for cancer therapy. J. Mol. Med. (Berl.), 2005, 83(12), 955-963. [http://dx.doi.org/ 10.1007/s00109-005-0705-x]. [PMID: 16283145].
[31]
Mullard, A. Protein-protein interaction inhibitors get into the groove. Nat. Rev. Drug Discov., 2012, 11(3), 173-175. [http://dx.doi.org/ 10.1038/nrd3680].
[32]
Rao, V.S.; Srinivas, K.; Sujini, G.N.; Kumar, G.N. Protein-protein interaction detection: Methods and analysis. Int. J. Proteomics, 2014, 2014, 147648. [http://dx.doi.org/ 10.1155/2014/147648]. [PMID: 24693427].
[33]
Mason, J.M. Design and development of peptides and peptide mimetics as antagonists for therapeutic intervention. Future Med. Chem., 2010, 2(12), 1813-1822. [http://dx.doi.org/ 10.4155/ fmc.10.259]. [PMID: 21428804].
[34]
Demange, L.; Abdellah, F.N.; Lozach, O.; Ferandin, Y.; Gresh, N.; Meijer, L.; Galons, H. Potent inhibitors of CDK5 derived from roscovitine: synthesis, biological evaluation and molecular modelling. Bioorg. Med. Chem. Lett., 2013, 23(1), 125-131. [http://dx.doi.org/ 10.1016/j.bmcl.2012.10.141]. [PMID: 23218601].
[35]
Baxter, D.; Ullman, C.G.; Mason, J.M. Library construction, selection and modification strategies to generate therapeutic peptide-based modulators of protein-protein interactions. Future Med. Chem., 2014, 6(18), 2073-2092. [http://dx.doi.org/ 10.4155/ fmc.14.134]. [PMID: 25531969].
[36]
Jochim, A.L.; Arora, P.S. Systematic analysis of helical protein interfaces reveals targets for synthetic inhibitors. ACS Chem. Biol., 2010, 5(10), 919-923. [http://dx.doi.org/ 10.1021/cb1001747]. [PMID: 20712375].
[37]
Moradi, S.; Soltani, S.; Ansari, A.M.; Sardari, S. Peptidomimetics and their applications in antifungal drug design. Antiinfect. Agents Med. Chem., 2009, 8, 327-344. [http://dx.doi.org/ 10.2174/ 187152109789760216].
[38]
Sillerud, L.O.; Larson, R.S. Design and structure of peptide and peptidomimetic antagonists of protein-protein interaction. Curr. Protein Pept. Sci., 2005, 6(2), 151-169. [http://dx.doi.org/ 10.2174/1389203053545462]. [PMID: 15853652].
[39]
Lao, B.B.; Drew, K.; Guarracino, D.A.; Brewer, T.F.; Heindel, D.W.; Bonneau, R.; Arora, P.S. Rational design of topographical helix mimics as potent inhibitors of protein-protein interactions. J. Am. Chem. Soc., 2014, 136(22), 7877-7888. [http://dx.doi.org/ 10.1021/ja502310r]. [PMID: 24972345].
[40]
Cumming, J.N.; Smith, E.M.; Wang, L.; Misiaszek, J.; Durkin, J.; Pan, J.; Iserloh, U.; Wu, Y.; Zhu, Z.; Strickland, C.; Voigt, J.; Chen, X.; Kennedy, M.E.; Kuvelkar, R.; Hyde, L.A.; Cox, K.; Favreau, L.; Czarniecki, M.F.; Greenlee, W.J.; McKittrick, B.A.; Parker, E.M.; Stamford, A.W. Structure based design of iminohydantoin BACE1 inhibitors: Identification of an orally available, centrally active BACE1 inhibitor. Bioorg. Med. Chem. Lett., 2012, 22(7), 2444-2449. [http://dx.doi.org/ 10.1016/j.bmcl.2012.02.013]. [PMID: 22390835].
[41]
Volkman, H.M.; Rutledge, S.E.; Schepartz, A. Binding mode and transcriptional activation potential of high affinity ligands for the CBP KIX domain. J. Am. Chem. Soc., 2005, 127(13), 4649-4658. [http://dx.doi.org/ 10.1021/ja042761y]. [PMID: 15796530].
[42]
Phan, T.; Nguyen, H.D.; Göksel, H.; Möcklinghoff, S.; Brunsveld, L. Phage display selection of miniprotein binders of the Estrogen Receptor. Chem. Commun. (Camb.), 2010, 46(43), 8207-8209. [http://dx.doi.org/ 10.1039/c0cc02727h]. [PMID: 20871934].
[43]
Leduc, A-M.; Trent, J.O.; Wittliff, J.L.; Bramlett, K.S.; Briggs, S.L.; Chirgadze, N.Y.; Wang, Y.; Burris, T.P.; Spatola, A.F. Helix-stabilized cyclic peptides as selective inhibitors of steroid receptor-coactivator interactions. Proc. Natl. Acad. Sci. USA, 2003, 100(20), 11273-11278. [http://dx.doi.org/ 10.1073/pnas.1934759100]. [PMID: 13679575].
[44]
Chorev, M.; Roubini, E.; McKee, R.L.; Gibbons, S.W.; Goldman, M.E.; Caulfield, M.P.; Rosenblatt, M. Cyclic parathyroid hormone related protein antagonists: Lysine 13 to aspartic acid 17 [i to (i + 4)] side chain to side chain lactamization. Biochemistry, 1991, 30(24), 5968-5974. [http://dx.doi.org/ 10.1021/bi00238a022]. [PMID: 1646005].
[45]
Blackwell, H.E.; Grubbs, R.H. Highly efficient synthesis of covalently cross‐linked peptide helices by ring‐closing metathesis. Angew. Chem. Int. Ed. Engl., 1998, 37(23), 3281-3284. [http://dx.doi.org/10.1002/(SICI)1521-3773(19981217)37:23<3281:AID-ANIE3281>3.0.CO;2-V]. [PMID: 29711420].
[46]
Patgiri, A.; Jochim, A.L.; Arora, P.S. A hydrogen bond surrogate approach for stabilization of short peptide sequences in α-helical conformation. Acc. Chem. Res., 2008, 41(10), 1289-1300. [http://dx.doi.org/ 10.1021/ar700264k]. [PMID: 18630933].
[47]
Moritz, W.; Helmut, H.; Stefan, A.; Dieter, S. β-Peptides as inhibitors of small-intestinal cholesterol and fat absorption. Helv. Chim. Acta, 1999, 82, 1774-1783. [http://dx.doi.org/ 10.1002/(SICI)1522-2675(19991006)82:10<1774:AID-HLCA1774>3.0.CO;2-O].
[48]
Guharoy, M.; Chakrabarti, P. Secondary structure based analysis and classification of biological interfaces: identification of binding motifs in protein-protein interactions. Bioinformatics, 2007, 23(15), 1909-1918. [http://dx.doi.org/ 10.1093/bioinformatics/btm274]. [PMID: 17510165].
[49]
Villar, E.A.; Beglov, D.; Chennamadhavuni, S.; Porco, J.A., Jr; Kozakov, D.; Vajda, S.; Whitty, A. How proteins bind macrocycles. Nat. Chem. Biol., 2014, 10(9), 723-731. [http://dx.doi.org/ 10.1038/nchembio.1584]. [PMID: 25038790].
[50]
Sperandio, O.; Reynès, C.H.; Camproux, A-C.; Villoutreix, B.O. Rationalizing the chemical space of protein-protein interaction inhibitors. Drug Discov. Today, 2010, 15(5-6), 220-229. [http://dx.doi.org/ 10.1016/j.drudis.2009.11.007]. [PMID: 19969101].
[51]
Murray, J.K.; Gellman, S.H. Targeting protein-protein interactions: Lessons from p53/MDM2. Biopolymers, 2007, 88(5), 657-686. [http://dx.doi.org/ 10.1002/bip.20741]. [PMID: 17427181].
[52]
Wang, S.; Zhao, Y.; Aguilar, A.; Bernard, D.; Yang, C-Y. Targeting the MDM2–p53 protein–protein interaction for new cancer therapy: progress and challenges. Cold Spring Harb. Perspect. Med., 2017, 7(5), a026245. [http://dx.doi.org/ 10.1101/cshperspect. a026245]. [PMID: 28270530].
[53]
Berg, T. Small-molecule inhibitors of protein–protein interactions.In: Protein-protein Complexes; Analysis, Modeling and Drug Design, 2010, pp. 318-339. [http://dx.doi.org/ 10.1142/9781848-163409_0012]
[54]
Srinivasula, S.M.; Hegde, R.; Saleh, A.; Datta, P.; Shiozaki, E.; Chai, J.; Lee, R.A.; Robbins, P.D.; Fernandes-Alnemri, T.; Shi, Y.; Alnemri, E.S. A conserved XIAP-interaction motif in caspase-9 and Smac/DIABLO regulates caspase activity and apoptosis. Nature, 2001, 410(6824), 112-116. [http://dx.doi.org/ 10.1038/3506-5125]. [PMID: 11242052].
[55]
Sgrignani, J.; Garofalo, M.; Matkovic, M.; Merulla, J.; Catapano, C.V.; Cavalli, A. Structural biology of STAT3 and its implications for anticancer therapies development. Int. J. Mol. Sci., 2018, 19(6), 1591-1604. [http://dx.doi.org/ 10.3390/ijms19061591]. [PMID: 29843450].
[56]
Phiel, C.J.; Wilson, C.A.; Lee, V.M.Y.; Klein, P.S. GSK-3α regulates production of Alzheimer’s disease amyloid-β peptides. Nature, 2003, 423(6938), 435-439. [http://dx.doi.org/ 10.1038/nature 01640]. [PMID: 12761548].
[57]
Heinemann, U.; Gawinecka, J.; Schmidt, C.; Zerr, I. Differential diagnosis of rapid progressive dementia. Eur. Neurol. Rev., 2010, 5, 21-28. [http://dx.doi.org/ 10.17925/ENR.2010.05.02.21].
[58]
Bruggink, K.A.; Müller, M.; Kuiperij, H.B.; Verbeek, M.M. Methods for analysis of amyloid-β aggregates. J. Alzheimers Dis., 2012, 28(4), 735-758. [http://dx.doi.org/ 10.3233/JAD-2011-111421]. [PMID: 22156047].
[59]
Kumari, S.; Mishra, C.B.; Idrees, D.; Prakash, A.; Yadav, R.; Hassan, M.I.; Tiwari, M. Design, synthesis, in silico and biological evaluation of novel 2-(4-(4-substituted piperazin-1-yl)benzylidene)hydrazine carboxamides. Mol. Divers., 2017, 21(1), 163-174. [http://dx.doi.org/ 10.1007/s11030-016-9714-7]. [PMID: 28039637].
[60]
Hansen, R.A.; Gartlehner, G.; Webb, A.P.; Morgan, L.C.; Moore, C.G.; Jonas, D.E. Efficacy and safety of donepezil, galantamine, and rivastigmine for the treatment of Alzheimer’s disease: A systematic review and meta-analysis. Clin. Interv. Aging, 2008, 3(2), 211-225. [PMID: 18686744].
[61]
Reitz, C.; Mayeux, R. Alzheimer disease: epidemiology, diagnostic criteria, risk factors and biomarkers. Biochem. Pharmacol., 2014, 88(4), 640-651. [http://dx.doi.org/ 10.1016/j.bcp.2013.12.024]. [PMID: 24398425].
[62]
Cummings, J.L.; Vinters, H.V.; Cole, G.M.; Khachaturian, Z.S. Alzheimer’s disease: etiologies, pathophysiology, cognitive reserve, and treatment opportunities. Neurology,, 1998, 51(1), (Suppl. 1), S2-S17. [http://dx.doi.org/ 10.1212/WNL.51.1_Suppl_1.S2]. [PMID:9674758].
[63]
Salomone, S.; Caraci, F.; Leggio, G.M.; Fedotova, J.; Drago, F. New pharmacological strategies for treatment of Alzheimer’s disease: focus on disease modifying drugs. Br. J. Clin. Pharmacol., 2012, 73(4), 504-517. [http://dx.doi.org/ 10.1111/j.1365-2125.2011.04134.x]. [PMID: 22035455].
[64]
Alvarez, A.; Opazo, C.; Alarcón, R.; Garrido, J.; Inestrosa, N.C. Acetylcholinesterase promotes the aggregation of amyloid-beta-peptide fragments by forming a complex with the growing fibrils. J. Mol. Biol., 1997, 272(3), 348-361. [http://dx.doi.org/ 10.1006/jmbi.1997.1245]. [PMID: 9325095].
[65]
Zlokovic, B.V. Clearing amyloid through the blood-brain barrier. J. Neurochem., 2004, 89(4), 807-811. [http://dx.doi.org/ 10.1111/j.1471-4159.2004.02385.x]. [PMID: 15140180].
[66]
Basha, S.J.; Mohan, P.; Yeggoni, D.P.; Babu, Z.R.; Kumar, P.B.; Rao, A.D.; Subramanyam, R.; Damu, A.G. New flavone-cyanoacetamide hybrids with a combination of cholinergic, antioxidant, modulation of β-amyloid aggregation, and neuroprotection properties as innovative multifunctional therapeutic candidates for alzheimer’s disease and unraveling their mechanism of action with acetylcholinesterase. Mol. Pharm., 2018, 15(6), 2206-2223. [http://dx.doi.org/ 10.1021/acs.molpharmaceut.8b00041]. [PMID: 29745222].
[67]
Llorens-Martín, M.; Jurado, J.; Hernández, F.; Avila, J. GSK-3β, A pivotal kinase in Alzheimer disease. Front. Mol. Neurosci., 2014, 7, 46. [PMID: 24904272].
[68]
Lane, R.M.; Kivipelto, M.; Greig, N.H. Acetylcholinesterase and its inhibition in Alzheimer disease. Clin. Neuropharmacol., 2004, 27(3), 141-149. [http://dx.doi.org/ 10.1097/00002826-200405000-00011]. [PMID: 15190239].
[69]
Miguel-Hidalgo, J.J.; Paul, I.A.; Wanzo, V.; Banerjee, P.K. Memantine prevents cognitive impairment and reduces Bcl-2 and caspase 8 immunoreactivity in rats injected with amyloid β1-40. Eur. J. Pharmacol., 2012, 692(1-3), 38-45. [http://dx.doi.org/ 10.1016/j.ejphar.2012.07.032]. [PMID: 22824463].
[70]
Cottrell, D.A.; Borthwick, G.M.; Johnson, M.A.; Ince, P.G.; Turnbull, D.M. The role of cytochrome c oxidase deficient hippocampal neurones in Alzheimer’s disease. Neuropathol. Appl. Neurobiol., 2002, 28(5), 390-396. [http://dx.doi.org/ 10.1046/j.1365-2990.2002.00414.x]. [PMID: 12366820].
[71]
Nicolakakis, N.; Aboulkassim, T.; Ongali, B.; Lecrux, C.; Fernandes, P.; Rosa-Neto, P.; Tong, X.K.; Hamel, E. Complete rescue of cerebrovascular function in aged Alzheimer’s disease transgenic mice by antioxidants and pioglitazone, A peroxisome proliferator-activated receptor gamma agonist. J. Neurosci., 2008, 28(37), 9287-9296. [http://dx.doi.org/ 10.1523/JNEUROSCI.3348-08.2008]. [PMID: 18784309].
[72]
Wang, X.X.; Tan, M.S.; Yu, J.T.; Tan, L. Matrix metalloproteinases and their multiple roles in Alzheimer’s disease. BioMed Res. Int., 2014, 2014, 908636. [PMID: 25050378].
[73]
Swetha, R.; Gayen, C.; Kumar, D.; Singh, T.D.; Modi, G.; Singh, S.K. Biomolecular basis of matrix metallo proteinase-9 activity. Future Med. Chem., 2018, 10(9), 1093-1112. [http://dx.doi.org/ 10.4155/fmc-2017-0236]. [PMID: 29676173].
[74]
Tang, D.; Yeung, J.; Lee, K.Y.; Matsushita, M.; Matsui, H.; Tomizawa, K.; Hatase, O.; Wang, J.H. An isoform of the neuronal cyclin-dependent kinase 5 (CDK5) activator. J. Biol. Chem., 1995, 270(45), 26897-26903. [http://dx.doi.org/ 10.1074/jbc.270.45. 26897]. [PMID: 7592934].
[75]
Niethammer, M.; Smith, D.S.; Ayala, R.; Peng, J.; Ko, J.; Lee, M.S.; Morabito, M.; Tsai, L.H. NUDEL is a novel CDK5 substrate that associates with LIS1 and cytoplasmic dynein. Neuron, 2000, 28(3), 697-711. [http://dx.doi.org/ 10.1016/S0896-6273(00)00147-1]. [PMID: 11163260].
[76]
Larson, M.; Sherman, M.A.; Amar, F.; Nuvolone, M.; Schneider, J.A.; Bennett, D.A.; Aguzzi, A.; Lesné, S.E. The complex PrP(c)-Fyn couples human oligomeric Aβ with pathological tau changes in Alzheimer’s disease. J. Neurosci., 2012, 32(47), 16857-16871a. [http://dx.doi.org/ 10.1523/JNEUROSCI.1858-12.2012]. [PMID: 23175838].
[77]
Mapelli, M.; Massimiliano, L.; Crovace, C.; Seeliger, M.A.; Tsai, L-H.; Meijer, L.; Musacchio, A. Mechanism of CDK5/p25 binding by CDK inhibitors. J. Med. Chem., 2005, 48(3), 671-679. [http://dx.doi.org/ 10.1021/jm049323m]. [PMID: 15689152].
[78]
Tarricone, C.; Dhavan, R.; Peng, J.; Areces, L.B.; Tsai, L.H.; Musacchio, A. Structure and regulation of the CDK5-p25(nck5a) complex. Mol. Cell, 2001, 8(3), 657-669. [http://dx.doi.org/ 10.1016/S1097-2765(01)00343-4]. [PMID: 11583627].
[79]
Zhang, B.; Su, Z.C.; Tay, T.E.; Tan, V.B. Mechanism of CDK5 activation revealed by steered molecular dynamics simulations and energy calculations. J. Mol. Model., 2010, 16(6), 1159-1168. [http://dx.doi.org/ 10.1007/s00894-009-0629-4]. [PMID: 20013135].
[80]
Zhang, B.; Corbel, C.; Guéritte, F.; Couturier, C.; Bach, S.; Tan, V.B. An in silico approach for the discovery of CDK5/p25 interaction inhibitors. Biotechnol. J., 2011, 6(7), 871-881. [http://dx.doi.org/ 10.1002/biot.201100139]. [PMID: 21681969].
[81]
Kishimoto, A.; Kajikawa, N.; Tabuchi, H.; Shiota, M.; Nishizuka, Y. Calcium-dependent neural proteases, widespread occurrence of a species of protease active at lower concentrations of calcium. J. Biochem., 1981, 90(3), 889-892. [http://dx.doi.org/ 10.1093/ oxfordjournals.jbchem.a133547]. [PMID: 7031044].
[82]
Brown, B.A.; Nixon, R.A.; Strocchi, P.; Marotta, C.A. Characterization and comparison of neurofilament proteins from rat and mouse CNS. J. Neurochem., 1981, 36(1), 143-153. [http://dx.doi.org/ 10.1111/j.1471-4159.1981.tb02389.x]. [PMID: 7193240].
[83]
Nixon, R.A. Calcium-activated neutral proteinases as regulators of cellular function. Implications for Alzheimer’s disease pathogenesis. Ann. N. Y. Acad. Sci., 1989, 568, 198-208. [http://dx.doi.org/ 10.1111/j.1749-6632.1989.tb12509.x]. [PMID: 2560900].
[84]
Seubert, P.; Lee, K.; Lynch, G. Ischemia triggers NMDA receptor-linked cytoskeletal proteolysis in hippocampus. Brain Res., 1989, 492(1-2), 366-370. [http://dx.doi.org/ 10.1016/0006-8993(89) 90921-9]. [PMID: 2546656].
[85]
Arai, A.; Kessler, M.; Lee, K.; Lynch, G. Calpain inhibitors improve the recovery of synaptic transmission from hypoxia in hippocampal slices. Brain Res., 1990, 532(1-2), 63-68. [http://dx.doi.org/ 10.1016/0006-8993(90)91742-Y]. [PMID: 2178038].
[86]
Siman, R.; Noszek, J.C.; Kegerise, C. Calpain I activation is specifically related to excitatory amino acid induction of hippocampal damage. J. Neurosci., 1989, 9(5), 1579-1590. [http://dx.doi.org/ 10.1523/JNEUROSCI.09-05-01579.1989]. [PMID: 2542478].
[87]
Iwamoto, N.; Emson, P.C. Demonstration of neurofibrillary tangles in parvalbumin-immunoreactive interneurones in the cerebral cortex of Alzheimer-type dementia brain. Neurosci. Lett., 1991, 128(1), 81-84. [http://dx.doi.org/ 10.1016/0304-3940(91)90764-K]. [PMID: 1717900].
[88]
Iwamoto, N.; Thangnipon, W.; Crawford, C.; Emson, P.C. Localization of calpain immunoreactivity in senile plaques and in neurones undergoing neurofibrillary degeneration in Alzheimer’s disease. Brain Res., 1991, 561(1), 177-180. [http://dx.doi.org/ 10.1016/0006-8993(91)90766-O]. [PMID: 1797346].
[89]
Shimohama, S.; Suenaga, T.; Araki, W.; Yamaoaka, Y.; Shimizu, K.; Kimura, J. Presence of calpain II immunoreactivity in senile plaques in Alzheimer’s disease. Brain Res., 1991, 558(1), 105-108. [http://dx.doi.org/ 10.1016/0006-8993(91)90722-8]. [PMID: 1718565].
[90]
Patrick, G.N.; Zukerberg, L.; Nikolic, M.; de la Monte, S.; Dikkes, P.; Tsai, L.H. Conversion of p35 to p25 deregulates CDK5 activity and promotes neurodegeneration. Nature, 1999, 402(6762), 615-622. [http://dx.doi.org/ 10.1038/45159]. [PMID: 10604467].
[91]
Nath, R.; Davis, M.; Probert, A.W.; Kupina, N.C.; Ren, X.; Schielke, G.P.; Wang, K.K. Processing of CDK5 activator p35 to its truncated form (p25) by calpain in acutely injured neuronal cells. Biochem. Biophys. Res. Commun., 2000, 274(1), 16-21. [http://dx.doi.org/ 10.1006/bbrc.2000.3070]. [PMID: 10903889].
[92]
Ahlijanian, M.K.; Barrezueta, N.X.; Williams, R.D.; Jakowski, A.; Kowsz, K.P.; McCarthy, S.; Coskran, T.; Carlo, A.; Seymour, P.A.; Burkhardt, J.E.; Nelson, R.B.; McNeish, J.D. Hyperphosphorylated tau and neurofilament and cytoskeletal disruptions in mice overexpressing human p25, an activator of CDK5. Proc. Natl. Acad. Sci. USA, 2000, 97(6), 2910-2915. [http://dx.doi.org/ 10.1073/ pnas.040577797]. [PMID: 10706614].
[93]
Saitoh, T.; Masliah, E.; Jin, L.W.; Cole, G.M.; Wieloch, T.; Shapiro, I.P. Protein kinases and phosphorylation in neurologic disorders and cell death. Lab. Invest., 1991, 64(5), 596-616. [PMID: 2030574].
[94]
Rapoport, M.; Ferreira, A. PD98059 prevents neurite degeneration induced by fibrillar β-amyloid in mature hippocampal neurons. J. Neurochem., 2000, 74(1), 125-133. [http://dx.doi.org/ 10.1046/j. 1471-4159.2000.0740125.x]. [PMID: 10617113].
[95]
Canu, N.; Dus, L.; Barbato, C.; Ciotti, M.T.; Brancolini, C.; Rinaldi, A.M.; Novak, M.; Cattaneo, A.; Bradbury, A.; Calissano, P. Tau cleavage and dephosphorylation in cerebellar granule neurons undergoing apoptosis. J. Neurosci., 1998, 18(18), 7061-7074. [http://dx.doi.org/10.1523/JNEUROSCI.18-18-07061.1998]. [PMID: 9736630].
[96]
Park, S.Y.; Ferreira, A. The generation of a 17 kDa neurotoxic fragment: An alternative mechanism by which tau mediates β-amyloid-induced neurodegeneration. J. Neurosci., 2005, 25(22), 5365-5375. [http://dx.doi.org/ 10.1523/JNEUROSCI.1125-05. 2005]. [PMID: 15930385].
[97]
Liang, B.; Duan, B.Y.; Zhou, X.P.; Gong, J.X.; Luo, Z.G. Calpain activation promotes BACE1 expression, amyloid precursor protein processing, and amyloid plaque formation in a transgenic mouse model of Alzheimer disease. J. Biol. Chem., 2010, 285(36), 27737-27744. [http://dx.doi.org/ 10.1074/jbc.M110.117960]. [PMID: 20595388].
[98]
Liang, Z.; Liu, F.; Grundke-Iqbal, I.; Iqbal, K.; Gong, C.X. Down-regulation of cAMP-dependent protein kinase by over-activated calpain in Alzheimer disease brain. J. Neurochem., 2007, 103(6), 2462-2470. [http://dx.doi.org/ 10.1111/j.1471-4159.2007.04942.x]. [PMID: 17908236].
[99]
Saftig, P.; Peters, C.; von Figura, K.; Craessaerts, K.; Van Leuven, F.; De Strooper, B. Amyloidogenic processing of human amyloid precursor protein in hippocampal neurons devoid of cathepsin D. J. Biol. Chem., 1996, 271(44), 27241-27244. [http://dx.doi.org/ 10.1074/jbc.271.44.27241]. [PMID: 8910296].
[100]
Citron, M.; Diehl, T.S.; Capell, A.; Haass, C.; Teplow, D.B.; Selkoe, D.J. Inhibition of amyloid β-protein production in neural cells by the serine protease inhibitor AEBSF. Neuron, 1996, 17(1), 171-179. [http://dx.doi.org/ 10.1016/S0896-6273(00)80290-1]. [PMID: 8755488].
[101]
Steinhilb, M.L.; Turner, R.S.; Gaut, J.R. The protease inhibitor, MG132, blocks maturation of the amyloid precursor protein Swedish mutant preventing cleavage by beta-Secretase. J. Biol. Chem., 2001, 276(6), 4476-4484. [http://dx.doi.org/ 10.1074/jbc. M008793200]. [PMID: 11084038].
[102]
Sinha, S.; Anderson, J.P.; Barbour, R.; Basi, G.S.; Caccavello, R.; Davis, D.; Doan, M.; Dovey, H.F.; Frigon, N.; Hong, J.; Jacobson-Croak, K.; Jewett, N.; Keim, P.; Knops, J.; Lieberburg, I.; Power, M.; Tan, H.; Tatsuno, G.; Tung, J.; Schenk, D.; Seubert, P.; Suomensaari, S.M.; Wang, S.; Walker, D.; Zhao, J.; McConlogue, L.; John, V. Purification and cloning of amyloid precursor protein β-secretase from human brain. Nature, 1999, 402(6761), 537-540. [http://dx.doi.org/ 10.1038/990114]. [PMID: 10591214].
[103]
Hong, L.; Koelsch, G.; Lin, X.; Wu, S.; Terzyan, S.; Ghosh, A.K.; Zhang, X.C.; Tang, J. Structure of the protease domain of memapsin 2 (β-secretase) complexed with inhibitor. Science, 2000, 290(5489), 150-153. [http://dx.doi.org/ 10.1126/science.290. 5489.150]. [PMID: 11021803].
[104]
Vetrivel, K.S.; Zhang, Y.W.; Xu, H.; Thinakaran, G. Pathological and physiological functions of presenilins. Mol. Neurodegener., 2006, 1, 4. [http://dx.doi.org/ 10.1186/1750-1326-1-4]. [PMID: 16930451].
[105]
Walter, J.; Fluhrer, R.; Hartung, B.; Willem, M.; Kaether, C.; Capell, A.; Lammich, S.; Multhaup, G.; Haass, C. Phosphorylation regulates intracellular trafficking of β-secretase. J. Biol. Chem., 2001, 276(18), 14634-14641. [http://dx.doi.org/ 10.1074/jbc. M01111-6200]. [PMID: 11278841].
[106]
Haniu, M.; Denis, P.; Young, Y.; Mendiaz, E.A.; Fuller, J.; Hui, J.O.; Bennett, B.D.; Kahn, S.; Ross, S.; Burgess, T.; Katta, V.; Rogers, G.; Vassar, R.; Citron, M. Characterization of Alzheimer’s beta -secretase protein BACE. A pepsin family member with unusual properties. J. Biol. Chem., 2000, 275(28), 21099-21106. [http://dx.doi.org/ 10.1074/jbc.M002095200]. [PMID: 10887202].
[107]
Westmeyer, G.G.; Willem, M.; Lichtenthaler, S.F.; Lurman, G.; Multhaup, G.; Assfalg-Machleidt, I.; Reiss, K.; Saftig, P.; Haass, C. Dimerization of β-site β-amyloid precursor protein-cleaving enzyme. J. Biol. Chem., 2004, 279(51), 53205-53212. [http://dx.doi.org/ 10.1074/jbc.M410378200]. [PMID: 15485862].
[108]
Chakraborty, S.; Kumar, S.; Basu, S. Conformational transition in the substrate binding domain of β-secretase exploited by NMA and its implication in inhibitor recognition: BACE1-myricetin a case study. Neurochem. Int., 2011, 58(8), 914-923. [http://dx.doi.org/ 10.1016/j.neuint.2011.02.021]. [PMID: 21354237].
[109]
Yan, R.; Bienkowski, M.J.; Shuck, M.E.; Miao, H.; Tory, M.C.; Pauley, A.M.; Brashier, J.R.; Stratman, N.C.; Mathews, W.R.; Buhl, A.E.; Carter, D.B.; Tomasselli, A.G.; Parodi, L.A.; Heinrikson, R.L.; Gurney, M.E. Membrane-anchored aspartyl protease with Alzheimer’s disease β-secretase activity. Nature, 1999, 402(6761), 533-537. [http://dx.doi.org/ 10.1038/990107]. [PMID: 10591213].
[110]
Lahiri, D.K.; Maloney, B.; Ge, Y.W. Functional domains of the BACE1 and BACE2 promoters and mechanisms of transcriptional suppression of the BACE2 promoter in normal neuronal cells. J. Mol. Neurosci., 2006, 29(1), 65-80. [http://dx.doi.org/ 10.1385/JMN:29:1:65]. [PMID: 16757811].
[111]
Venugopal, C.; Demos, C.M.; Rao, K.S.; Pappolla, M.A.; Sambamurti, K. Beta-secretase: Structure, function, and evolution. CNS Neurol. Disord. Drug Targets, 2008, 7(3), 278-294. [http://dx.doi.org/10.2174/187152708784936626]. [PMID: 18673212].
[112]
Huse, J.T.; Pijak, D.S.; Leslie, G.J.; Lee, V.M.; Doms, R.W. Maturation and endosomal targeting of beta-site amyloid precursor protein-cleaving enzyme. The Alzheimer’s disease beta-secretase. J. Biol. Chem., 2000, 275(43), 33729-33737. [http://dx.doi.org/ 10.1074/jbc.M004175200]. [PMID: 10924510].
[113]
Capell, A.; Steiner, H.; Willem, M.; Kaiser, H.; Meyer, C.; Walter, J.; Lammich, S.; Multhaup, G.; Haass, C. Maturation and pro-peptide cleavage of beta-secretase. J. Biol. Chem., 2000, 275(40), 30849-30854. [http://dx.doi.org/ 10.1074/jbc.M003202200]. [PMID: 10801872].
[114]
Riemenschneider, M.; Klopp, N.; Xiang, W.; Wagenpfeil, S.; Vollmert, C.; Müller, U.; Förstl, H.; Illig, T.; Kretzschmar, H.; Kurz, A. Prion protein codon 129 polymorphism and risk of Alzheimer disease. Neurology, 2004, 63(2), 364-366. [http://dx.doi.org/10.1212/01.WNL.0000130198.72589.69]. [PMID: 15277640].
[115]
He, W.; Lu, Y.; Qahwash, I.; Hu, X.Y.; Chang, A.; Yan, R. Reticulon family members modulate BACE1 activity and amyloid-beta peptide generation. Nat. Med., 2004, 10(9), 959-965. [http://dx.doi.org/ 10.1038/nm1088]. [PMID: 15286784].
[116]
Hattori, C.; Asai, M.; Oma, Y.; Kino, Y.; Sasagawa, N.; Saido, T.C.; Maruyama, K.; Ishiura, S. BACE1 interacts with nicastrin. Biochem. Biophys. Res. Commun., 2002, 293(4), 1228-1232. [http://dx.doi.org/ 10.1016/S0006-291X(02)00351-0]. [PMID: 12054507].
[117]
Hébert, S.S.; Bourdages, V.; Godin, C.; Ferland, M.; Carreau, M.; Lévesque, G. Presenilin-1 interacts directly with the beta-site amyloid protein precursor cleaving enzyme (BACE1). Neurobiol. Dis., 2003, 13(3), 238-245. [http://dx.doi.org/ 10.1016/S0969-9961(03)00035-4]. [PMID: 12901838].
[118]
Bush, A.I.; Masters, C.L.; Tanzi, R.E. Copper, beta-amyloid, and Alzheimer’s disease: Tapping a sensitive connection. Proc. Natl. Acad. Sci. USA, 2003, 100(20), 11193-11194. [http://dx.doi.org/ 10.1073/pnas.2135061100]. [PMID: 14506299].
[119]
He, X.; Li, F.; Chang, W.P.; Tang, J. GGA proteins mediate the recycling pathway of memapsin 2 (BACE). J. Biol. Chem., 2005, 280(12), 11696-11703. [http://dx.doi.org/ 10.1074/jbc.M411296200]. [PMID: 15615712].
[120]
Xie, J.; Guo, Q. PAR-4 is involved in regulation of beta-secretase cleavage of the Alzheimer amyloid precursor protein. J. Biol. Chem., 2005, 280(14), 13824-13832. [http://dx.doi.org/ 10.1074/jbc.M411933200]. [PMID: 15671026].
[121]
Hussain, I.; Powell, D.J.; Howlett, D.R.; Chapman, G.A.; Gilmour, L.; Murdock, P.R.; Tew, D.G.; Meek, T.D.; Chapman, C.; Schneider, K.; Ratcliffe, S.J.; Tattersall, D.; Testa, T.T.; Southan, C.; Ryan, D.M.; Simmons, D.L.; Walsh, F.S.; Dingwall, C.; Christie, G. ASP1 (BACE2) cleaves the amyloid precursor protein at the β-secretase site. Mol. Cell. Neurosci., 2000, 16(5), 609-619. [http://dx.doi.org/ 10.1006/mcne.2000.0884]. [PMID: 11083922].
[122]
Laird, F.M.; Cai, H.; Savonenko, A.V.; Farah, M.H.; He, K.; Melnikova, T.; Wen, H.; Chiang, H-C.; Xu, G.; Koliatsos, V.E.; Borchelt, D.R.; Price, D.L.; Lee, H.K.; Wong, P.C. BACE1, a major determinant of selective vulnerability of the brain to amyloid-β amyloidogenesis, is essential for cognitive, emotional, and synaptic functions. J. Neurosci., 2005, 25(50), 11693-11709. [http://dx.doi.org/ 10.1523/JNEUROSCI.2766-05.2005]. [PMID: 16354928].
[123]
Kumar, D.; Ganeshpurkar, A.; Kumar, D.; Modi, G.; Gupta, S.K.; Singh, S.K. Secretase inhibitors for the treatment of Alzheimer’s disease: Long road ahead. Eur. J. Med. Chem., 2018, 148, 436-452. [http://dx.doi.org/ 10.1016/j.ejmech.2018.02.035]. [PMID: 29477076].
[124]
Roberds, S.L.; Anderson, J.; Basi, G.; Bienkowski, M.J.; Branstetter, D.G.; Chen, K.S.; Freedman, S.B.; Frigon, N.L.; Games, D.; Hu, K.; Johnson-Wood, K.; Kappenman, K.E.; Kawabe, T.T.; Kola, I.; Kuehn, R.; Lee, M.; Liu, W.; Motter, R.; Nichols, N.F.; Power, M.; Robertson, D.W.; Schenk, D.; Schoor, M.; Shopp, G.M.; Shuck, M.E.; Sinha, S.; Svensson, K.A.; Tatsuno, G.; Tintrup, H.; Wijsman, J.; Wright, S.; McConlogue, L. BACE knockout mice are healthy despite lacking the primary β-secretase activity in brain: Implications for Alzheimer’s disease therapeutics. Hum. Mol. Genet., 2001, 10(12), 1317-1324. [http://dx.doi.org/ 10.1093/hmg/10.12.1317]. [PMID: 11406613].
[125]
Holsinger, R.M.; McLean, C.A.; Beyreuther, K.; Masters, C.L.; Evin, G. Increased expression of the amyloid precursor β-secretase in Alzheimer’s disease. Ann. Neurol., 2002, 51(6), 783-786. [http://dx.doi.org/ 10.1002/ana.10208]. [PMID: 12112088].
[126]
Sullivan, S.E.; Dillon, G.M.; Sullivan, J.M.; Ho, A. Mint proteins are required for synaptic activity-dependent amyloid precursor protein (APP) trafficking and amyloid β generation. J. Biol. Chem., 2014, 289(22), 15374-15383. [http://dx.doi.org/ 10.1074/jbc.M113.541003]. [PMID: 24742670].
[127]
Hill, K.; Li, Y.; Bennett, M.; McKay, M.; Zhu, X.; Shern, J.; Torre, E.; Lah, J.J.; Levey, A.I.; Kahn, R.A. Munc18 interacting proteins: ADP-ribosylation factor-dependent coat proteins that regulate the traffic of β-Alzheimer’s precursor protein. J. Biol. Chem., 2003, 278(38), 36032-36040. [http://dx.doi.org/ 10.1074/jbc.M301632200]. [PMID: 12842896].
[128]
Belluti, F.; Piazzi, L.; Bisi, A.; Gobbi, S.; Bartolini, M.; Cavalli, A.; Valenti, P.; Rampa, A. Design, synthesis, and evaluation of benzophenone derivatives as novel acetylcholinesterase inhibitors. Eur. J. Med. Chem., 2009, 44(3), 1341-1348. [http://dx.doi.org/ 10.1016/j.ejmech.2008.02.035]. [PMID: 18396354].
[129]
Xie, X.; Yan, X.; Wang, Z.; Zhou, H.; Diao, W.; Zhou, W.; Long, J.; Shen, Y. Open-closed motion of Mint2 regulates APP metabolism. J. Mol. Cell Biol., 2013, 5(1), 48-56. [http://dx.doi.org/ 10.1093/jmcb/mjs033]. [PMID: 22730553].
[130]
Müller, U.C.; Deller, T.; Korte, M. Not just amyloid: physiological functions of the amyloid precursor protein family. Nat. Rev. Neurosci., 2017, 18(5), 281-298. [http://dx.doi.org/ 10.1038/nrn.2017.29]. [PMID: 28360418].
[131]
Rogelj, B.; Mitchell, J.C.; Miller, C.C.J.; McLoughlin, D.M. The X11/Mint family of adaptor proteins. Brain Res. Brain Res. Rev., 2006, 52(2), 305-315. [http://dx.doi.org/ 10.1016/j. brainresrev.2006.04.005]. [PMID: 16764936].
[132]
Lee, J-H.; Lau, K.F.; Perkinton, M.S.; Standen, C.L.; Shemilt, S.J.A.; Mercken, L.; Cooper, J.D.; McLoughlin, D.M.; Miller, C.C.J. The neuronal adaptor protein X11α reduces Abeta levels in the brains of Alzheimer’s APPswe Tg2576 transgenic mice. J. Biol. Chem., 2003, 278(47), 47025-47029. [http://dx.doi.org/ 10.1074/jbc.M300503200]. [PMID: 12970358].
[133]
Lee, J.H.; Lau, K.F.; Perkinton, M.S.; Standen, C.L.; Rogelj, B.; Falinska, A.; McLoughlin, D.M.; Miller, C.C.J. The neuronal adaptor protein X11β reduces amyloid β-protein levels and amyloid plaque formation in the brains of transgenic mice. J. Biol. Chem., 2004, 279(47), 49099-49104. [http://dx.doi.org/ 10.1074/jbc. M405602200]. [PMID: 15347685].
[134]
Araki, Y.; Tomita, S.; Yamaguchi, H.; Miyagi, N.; Sumioka, A.; Kirino, Y.; Suzuki, T. Novel cadherin-related membrane proteins, Alcadeins, enhance the X11-like protein-mediated stabilization of amyloid β-protein precursor metabolism. J. Biol. Chem., 2003, 278(49), 49448-49458. [http://dx.doi.org/ 10.1074/ jbc.M3060-24200]. [PMID: 12972431].
[135]
McLoughlin, D.M.; Standen, C.L.; Lau, K.F.; Ackerley, S.; Bartnikas, T.P.; Gitlin, J.D.; Miller, C.C.J. The neuronal adaptor protein X11α interacts with the copper chaperone for SOD1 and regulates SOD1 activity. J. Biol. Chem., 2001, 276(12), 9303-9307. [http://dx.doi.org/ 10.1074/jbc.M010023200]. [PMID: 11115513].
[136]
Biederer, T.; Südhof, T.C. Mints as adaptors. Direct binding to neurexins and recruitment of munc18. J. Biol. Chem., 2000, 275(51), 39803-39806. [http://dx.doi.org/ 10.1074/jbc. C000656200]. [PMID: 11036064].
[137]
Cumming, J.; Babu, S.; Huang, Y.; Carrol, C.; Chen, X.; Favreau, L.; Greenlee, W.; Guo, T.; Kennedy, M.; Kuvelkar, R.; Le, T.; Li, G.; McHugh, N.; Orth, P.; Ozgur, L.; Parker, E.; Saionz, K.; Stamford, A.; Strickland, C.; Tadesse, D.; Voigt, J.; Zhang, L.; Zhang, Q. Piperazine sulfonamide BACE1 inhibitors: design, synthesis, and in vivo characterization. Bioorg. Med. Chem. Lett., 2010, 20(9), 2837-2842. [http://dx.doi.org/ 10.1016/j.bmcl.2010.03.050]. [PMID: 20347593].
[138]
Long, J-F.; Feng, W.; Wang, R.; Chan, L-N.; Ip, F.C.F.; Xia, J.; Ip, N.Y.; Zhang, M. Autoinhibition of X11/Mint scaffold proteins revealed by the closed conformation of the PDZ tandem. Nat. Struct. Mol. Biol., 2005, 12(8), 722-728. [http://dx.doi.org/ 10.1038/nsmb958]. [PMID: 16007100].
[139]
Duquesne, A.E.; Ruijter, Md.; Brouwer, J.; Drijfhout, J.W.; Nabuurs, S.B.; Spronk, C.A.E.M.; Vuister, G.W.; Ubbink, M.; Canters, G.W. Solution structure of the second PDZ domain of the neuronal adaptor X11α and its interaction with the C-terminal peptide of the human copper chaperone for superoxide dismutase. J. Biomol. NMR, 2005, 32(3), 209-218. [http://dx.doi.org/ 10.1007/s10858-005-7333-1]. [PMID: 16132821].
[140]
Joshi, M.; Vargas, C.; Boisguerin, P.; Diehl, A.; Krause, G.; Schmieder, P.; Moelling, K.; Hagen, V.; Schade, M.; Oschkinat, H. Discovery of low-molecular-weight ligands for the AF6 PDZ domain. Angew. Chem. Int. Ed. Engl., 2006, 45(23), 3790-3795. [http://dx.doi.org/ 10.1002/anie.200503965]. [PMID: 16671149].
[141]
Manczak, M.; Calkins, M.J.; Reddy, P.H. Impaired mitochondrial dynamics and abnormal interaction of amyloid beta with mitochondrial protein Drp1 in neurons from patients with Alzheimer’s disease: implications for neuronal damage. Hum. Mol. Genet., 2011, 20(13), 2495-2509. [http://dx.doi.org/ 10.1093/hmg/ddr139]. [PMID: 21459773].
[142]
Chang, K.H.; Multani, P.S.; Sun, K.H.; Vincent, F.; de Pablo, Y.; Ghosh, S.; Gupta, R.; Lee, H.P.; Lee, H.G.; Smith, M.A.; Shah, K. Nuclear envelope dispersion triggered by deregulated CDK5 precedes neuronal death. Mol. Biol. Cell, 2011, 22(9), 1452-1462. [http://dx.doi.org/ 10.1091/mbc.e10-07-0654]. [PMID: 21389115].
[143]
Meuer, K.; Suppanz, I.E.; Lingor, P.; Planchamp, V.; Göricke, B.; Fichtner, L.; Braus, G.H.; Dietz, G.P.; Jakobs, S.; Bähr, M.; Weishaupt, J.H. Cyclin-dependent kinase 5 is an upstream regulator of mitochondrial fission during neuronal apoptosis. Cell Death Differ., 2007, 14(4), 651-661. [http://dx.doi.org/ 10.1038/sj.cdd.4402087]. [PMID: 17218957].
[144]
Velayos, J.L.; Irujo, A.; Cuadrado-Tejedor, M.; Paternain, B.; Moleres, F.J.; Ferrer, V. The cellular prion protein and its role in Alzheimer disease. Prion, 2009, 3(2), 110-117. [http://dx.doi.org/ 10.4161/pri.3.2.9135]. [PMID: 19556894].
[145]
Chen, S.; Yadav, S.P.; Surewicz, W.K. Interaction between human prion protein and amyloid-β (Abeta) oligomers: role OF N-terminal residues. J. Biol. Chem., 2010, 285(34), 26377-26383. [http://dx.doi.org/ 10.1074/jbc.M110.145516]. [PMID: 20576610].
[146]
Barry, A.E.; Klyubin, I.; Mc Donald, J.M.; Mably, A.J.; Farrell, M.A.; Scott, M.; Walsh, D.M.; Rowan, M.J. Alzheimer’s disease brain-derived amyloid-β-mediated inhibition of LTP in vivo is prevented by immunotargeting cellular prion protein. J. Neurosci., 2011, 31(20), 7259-7263. [http://dx.doi.org/10.1523/JNEUROSCI.6500-10.2011]. [PMID: 21593310].
[147]
Freir, D.B.; Nicoll, A.J.; Klyubin, I.; Panico, S.; Mc Donald, J.M.; Risse, E.; Asante, E.A.; Farrow, M.A.; Sessions, R.B.; Saibil, H.R.; Clarke, A.R.; Rowan, M.J.; Walsh, D.M.; Collinge, J. Interaction between prion protein and toxic amyloid β assemblies can be therapeutically targeted at multiple sites. Nat. Commun., 2011, 2, 336. [http://dx.doi.org/ 10.1038/ncomms1341]. [PMID: 21654636].
[148]
Renner, M.; Lacor, P.N.; Velasco, P.T.; Xu, J.; Contractor, A.; Klein, W.L.; Triller, A. Deleterious effects of amyloid beta oligomers acting as an extracellular scaffold for mGluR5. Neuron, 2010, 66(5), 739-754. [http://dx.doi.org/10.1016/j.neuron.2010.04.029]. [PMID: 20547131].
[149]
Albasanz, J.L.; Dalfó, E.; Ferrer, I.; Martín, M. Impaired metabotropic glutamate receptor/phospholipase C signaling pathway in the cerebral cortex in Alzheimer’s disease and dementia with Lewy bodies correlates with stage of Alzheimer’s-disease-related changes. Neurobiol. Dis., 2005, 20(3), 685-693. [http://dx.doi.org/ 10.1016/j.nbd.2005.05.001]. [PMID: 15949941].
[150]
Snyder, E.M.; Nong, Y.; Almeida, C.G.; Paul, S.; Moran, T.; Choi, E.Y.; Nairn, A.C.; Salter, M.W.; Lombroso, P.J.; Gouras, G.K.; Greengard, P. Regulation of NMDA receptor trafficking by amyloid-β. Nat. Neurosci., 2005, 8(8), 1051-1058. [http://dx.doi.org/ 10.1038/nn1503]. [PMID: 16025111].
[151]
Shankar, G.M.; Bloodgood, B.L.; Townsend, M.; Walsh, D.M.; Selkoe, D.J.; Sabatini, B.L. Natural oligomers of the Alzheimer amyloid-beta protein induce reversible synapse loss by modulating an NMDA-type glutamate receptor-dependent signaling pathway. J. Neurosci., 2007, 27(11), 2866-2875. [http://dx.doi.org/ 10.1523/JNEUROSCI.4970-06.2007]. [PMID: 17360908].
[152]
Lechward, K.; Awotunde, O.S.; Swiatek, W.; Muszyńska, G. Protein phosphatase 2A: Variety of forms and diversity of functions. Acta Biochim. Pol., 2001, 48(4), 921-933. [PMID: 11996003].
[153]
Janssens, V.; Goris, J. Protein phosphatase 2A: A highly regulated family of serine/threonine phosphatases implicated in cell growth and signalling. Biochem. J., 2001, 353(Pt 3), 417-439. [http://dx.doi.org/ 10.1042/bj3530417]. [PMID: 11171037].
[154]
Sontag, E.; Luangpirom, A.; Hladik, C.; Mudrak, I.; Ogris, E.; Speciale, S.; White, C.L., III Altered expression levels of the protein phosphatase 2A ABalphaC enzyme are associated with Alzheimer disease pathology. J. Neuropathol. Exp. Neurol., 2004, 63(4), 287-301. [http://dx.doi.org/ 10.1093/jnen/63.4.287]. [PMID: 15099019].
[155]
Gong, C.X.; Singh, T.J.; Grundke-Iqbal, I.; Iqbal, K. Phosphoprotein phosphatase activities in Alzheimer disease brain. J. Neurochem., 1993, 61(3), 921-927. [http://dx.doi.org/ 10.1111/j.1471-4159.1993.tb03603.x]. [PMID: 8395566].
[156]
Tanimukai, H.; Grundke-Iqbal, I.; Iqbal, K. Up-regulation of inhibitors of protein phosphatase-2A in Alzheimer’s disease. Am. J. Pathol., 2005, 166(6), 1761-1771. [http://dx.doi.org/ 10.1016/S0002-9440(10)62486-8]. [PMID: 15920161].
[157]
Voronkov, M.; Braithwaite, S.P.; Stock, J.B. Phosphoprotein phosphatase 2A: A novel druggable target for Alzheimer’s disease. Future Med. Chem., 2011, 3(7), 821-833. [http://dx.doi.org/ 10.4155/fmc.11.47]. [PMID: 21644827].
[158]
Kang, S.W.; Chae, H.Z.; Seo, M.S.; Kim, K.; Baines, I.C.; Rhee, S.G. Mammalian peroxiredoxin isoforms can reduce hydrogen peroxide generated in response to growth factors and tumor necrosis factor-alpha. J. Biol. Chem., 1998, 273(11), 6297-6302. [http://dx.doi.org/ 10.1074/jbc.273.11.6297]. [PMID: 9497357].
[159]
Cho, K.J.; Park, Y.; Khan, T.; Lee, J.H.; Kim, S.; Seok, J.H.; Chung, Y.B.; Cho, A.E.; Choi, Y.; Chang, T.S.; Kim, K.H. Crystal structure of dimeric human peroxiredoxin-1 C83S mutant. Bull. Korean Chem. Soc., 2015, 36, 1543-1545. [http://dx.doi.org/ 10.1002/bkcs.10284].
[160]
Chang, T.S.; Jeong, W.; Choi, S.Y.; Yu, S.; Kang, S.W.; Rhee, S.G. Regulation of peroxiredoxin I activity by Cdc2-mediated phosphorylation. J. Biol. Chem., 2002, 277(28), 25370-25376. [http://dx.doi.org/ 10.1074/jbc.M110432200]. [PMID: 11986303].
[161]
Sun, K.H.; de Pablo, Y.; Vincent, F.; Johnson, E.O.; Chavers, A.K.; Shah, K. Novel genetic tools reveal CDK5's major role in Golgi fragmentation in Alzheimer’s disease. Mol. Biol. Cell, 2008, 19(7), 3052-3069. [http://dx.doi.org/ 10.1091/mbc.e07-11-1106]. [PMID: 18480410].
[162]
Meijer, L.; Borgne, A.; Mulner, O.; Chong, J.P.; Blow, J.J.; Inagaki, N.; Inagaki, M.; Delcros, J.G.; Moulinoux, J.P. Biochemical and cellular effects of roscovitine, A potent and selective inhibitor of the cyclin-dependent kinases cdc2, CDK2 and CDK5. Eur. J. Biochem., 1997, 243(1-2), 527-536. [http://dx.doi.org/ 10.1111/j.1432-1033.1997.t01-2-00527.x]. [PMID: 9030781].
[163]
Ruan, J.; Xu, C.; Bian, C.; Lam, R.; Wang, J.P.; Kania, J.; Min, J.; Zang, J. Crystal structures of the coil 2B fragment and the globular tail domain of human lamin B1. FEBS Lett., 2012, 586(4), 314-318. [http://dx.doi.org/ 10.1016/j.febslet.2012.01.007]. [PMID: 22265972].
[164]
Yeh, C.H.; Kuo, P.L.; Wang, Y.Y.; Wu, Y.Y.; Chen, M.F.; Lin, D.Y.; Lai, T.H.; Chiang, H.S.; Lin, Y.H. SEPT12/SPAG4/LAMINB1 complexes are required for maintaining the integrity of the nuclear envelope in postmeiotic male germ cells. PLoS One, 2015, 10(3), e0120722. [http://dx.doi.org/ 10.1371/journal.pone.0120722]. [PMID: 25775403].
[165]
Black, W.; Vasiliou, V. The aldehyde dehydrogenase gene superfamily resource center. Hum. Genomics, 2009, 4(2), 136-142. [http://dx.doi.org/ 10.1186/1479-7364-4-2-136]. [PMID: 20038501].
[166]
Farrés, J.; Wang, T.T.; Cunningham, S.J.; Weiner, H. Investigation of the active site cysteine residue of rat liver mitochondrial aldehyde dehydrogenase by site-directed mutagenesis. Biochemistry, 1995, 34(8), 2592-2598. [http://dx.doi.org/ 10.1021/bi00008a025]. [PMID: 7873540].
[167]
Nikhil, K.; Viccaro, K.; Shah, K. Multifaceted regulation of ALDH1A1 by CDK5 in Alzheimer’s disease pathogenesis. Mol. Neurobiol., 2019, 56(2), 1366-1390. [PMID: 29948941].
[168]
Knudsen, K.A.; Rosand, J.; Karluk, D.; Greenberg, S.M. Clinical diagnosis of cerebral amyloid angiopathy: Validation of the Boston criteria. Neurology, 2001, 56(4), 537-539. [http://dx.doi.org/ 10.1212/WNL.56.4.537]. [PMID: 11222803].
[169]
Vinters, H.V. Cerebral amyloid angiopathy. A critical review. Stroke, 1987, 18(2), 311-324. [http://dx.doi.org/10.1161/01.STR.18.2.311]. [PMID: 3551211].
[170]
Hawkes, C.A.; Sullivan, P.M.; Hands, S.; Weller, R.O.; Nicoll, J.A.; Carare, R.O. Disruption of arterial perivascular drainage of amyloid-β from the brains of mice expressing the human APOE ε4 allele. PLoS One, 2012, 7, 1-11. [http://dx.doi.org/ 10.1371/journal.pone.0041636].
[171]
Zekonyte, J.; Sakai, K.; Nicoll, J.A.R.; Weller, R.O.; Carare, R.O. Quantification of molecular interactions between ApoE, amyloid-beta (Aβ) and laminin: Relevance to accumulation of Aβ in Alzheimer’s disease. Biochim. Biophys. Acta, 2016, 1862(5), 1047-1053. [http://dx.doi.org/ 10.1016/j.bbadis.2015.08.025]. [PMID: 26327683].
[172]
Yang, L.B.; Lindholm, K.; Yan, R.; Citron, M.; Xia, W.; Yang, X.L.; Beach, T.; Sue, L.; Wong, P.; Price, D.; Li, R.; Shen, Y. Elevated β-secretase expression and enzymatic activity detected in sporadic Alzheimer disease. Nat. Med., 2003, 9(1), 3-4. [http://dx.doi.org/ 10.1038/nm0103-3]. [PMID: 12514700].
[173]
Tarassishin, L.; Yin, Y.I.; Bassit, B.; Li, Y-M. Processing of Notch and amyloid precursor protein by γ-secretase is spatially distinct. Proc. Natl. Acad. Sci. USA, 2004, 101(49), 17050-17055. [http://dx.doi.org/ 10.1073/pnas.0408007101]. [PMID: 15563588].
[174]
Kojro, E.; Fahrenholz, F. The non-amyloidogenic pathway In: Structure and function of α-Secretases.Alzheimer’s Disease: Cellular and Molecular Aspects of Amyloid β, Springer,, 2005, pp. 105- 127. [http://dx.doi.org/ 10.1007/0-387-23226-5_5]
[175]
Hartmann, T.; Bieger, S.C.; Brühl, B.; Tienari, P.J.; Ida, N.; Allsop, D.; Roberts, G.W.; Masters, C.L.; Dotti, C.G.; Unsicker, K.; Beyreuther, K. Distinct sites of intracellular production for Alzheimer’s disease A β40/42 amyloid peptides. Nat. Med., 1997, 3(9), 1016-1020. [http://dx.doi.org/ 10.1038/nm0997-1016]. [PMID: 9288729].
[176]
Greenfield, J.P.; Tsai, J.; Gouras, G.K.; Hai, B.; Thinakaran, G.; Checler, F.; Sisodia, S.S.; Greengard, P.; Xu, H. Endoplasmic reticulum and trans-Golgi network generate distinct populations of Alzheimer β-amyloid peptides. Proc. Natl. Acad. Sci. USA, 1999, 96(2), 742-747. [http://dx.doi.org/ 10.1073/pnas.96.2.742]. [PMID: 9892704].
[177]
Koo, E.H.; Sisodia, S.S.; Archer, D.R.; Martin, L.J.; Weidemann, A.; Beyreuther, K.; Fischer, P.; Masters, C.L.; Price, D.L. Precursor of amyloid protein in Alzheimer disease undergoes fast anterograde axonal transport. Proc. Natl. Acad. Sci. USA, 1990, 87(4), 1561-1565. [http://dx.doi.org/ 10.1073/pnas.87.4.1561]. [PMID: 1689489].
[178]
Burdick, D.; Soreghan, B.; Kwon, M.; Kosmoski, J.; Knauer, M.; Henschen, A.; Yates, J.; Cotman, C.; Glabe, C. Assembly and aggregation properties of synthetic Alzheimer’s A4/beta amyloid peptide analogs. J. Biol. Chem., 1992, 267(1), 546-554. [PMID: 1730616].
[179]
Prior, R.; D’Urso, D.; Frank, R.; Prikulis, I.; Cleven, S.; Ihl, R.; Pavlakovic, G. Selective binding of soluble Abeta1-40 and Abeta1-42 to a subset of senile plaques. Am. J. Pathol., 1996, 148(6), 1749-1756. [PMID: 8669461].
[180]
Bitan, G.; Kirkitadze, M.D.; Lomakin, A.; Vollers, S.S.; Benedek, G.B.; Teplow, D.B. Amyloid β -protein (Abeta) assembly: Abeta 40 and Abeta 42 oligomerize through distinct pathways. Proc. Natl. Acad. Sci. USA, 2003, 100(1), 330-335. [http://dx.doi.org/ 10.1073/pnas.222681699]. [PMID: 12506200].
[181]
Haass, C.; Selkoe, D.J. Soluble protein oligomers in neurodegeneration: Lessons from the Alzheimer’s amyloid β-peptide. Nat. Rev. Mol. Cell Biol., 2007, 8(2), 101-112. [http://dx.doi.org/ 10.1038/nrm2101]. [PMID: 17245412].
[182]
Hartley, D.M.; Walsh, D.M.; Ye, C.P.; Diehl, T.; Vasquez, S.; Vassilev, P.M.; Teplow, D.B.; Selkoe, D.J. Protofibrillar intermediates of amyloid β-protein induce acute electrophysiological changes and progressive neurotoxicity in cortical neurons. J. Neurosci., 1999, 19(20), 8876-8884. [http://dx.doi.org/ 10.1523/JNEUROSCI.19-20-08876.1999]. [PMID: 10516307].
[183]
Lashuel, H.A.; Hartley, D.; Petre, B.M.; Walz, T.; Lansbury, P.T., Jr Neurodegenerative disease: Amyloid pores from pathogenic mutations. Nature, 2002, 418(6895), 291. [http://dx.doi.org/ 10.1038/418291a]. [PMID: 12124613].
[184]
Gong, Y.; Chang, L.; Viola, K.L.; Lacor, P.N.; Lambert, M.P.; Finch, C.E.; Krafft, G.A.; Klein, W.L. Alzheimer’s disease-affected brain: presence of oligomeric A β ligands (ADDLs) suggests a molecular basis for reversible memory loss. Proc. Natl. Acad. Sci. USA, 2003, 100(18), 10417-10422. [http://dx.doi.org/ 10.1073/pnas.1834302100]. [PMID: 12925731].
[185]
Lesné, S.; Koh, M.T.; Kotilinek, L.; Kayed, R.; Glabe, C.G.; Yang, A.; Gallagher, M.; Ashe, K.H. A specific amyloid-β protein assembly in the brain impairs memory. Nature, 2006, 440(7082), 352-357. [http://dx.doi.org/ 10.1038/nature04533]. [PMID: 16541076].
[186]
Podlisny, M.B.; Ostaszewski, B.L.; Squazzo, S.L.; Koo, E.H.; Rydell, R.E.; Teplow, D.B.; Selkoe, D.J. Aggregation of secreted amyloid beta-protein into sodium dodecyl sulfate-stable oligomers in cell culture. J. Biol. Chem., 1995, 270(16), 9564-9570. [http://dx.doi.org/ 10.1074/jbc.270.16.9564]. [PMID: 7721886].
[187]
Walsh, D.M.; Tseng, B.P.; Rydel, R.E.; Podlisny, M.B.; Selkoe, D.J. The oligomerization of amyloid β-protein begins intracellularly in cells derived from human brain. Biochemistry, 2000, 39(35), 10831-10839. [http://dx.doi.org/ 10.1021/bi001048s]. [PMID: 10978169].
[188]
Lansbury, P.T., Jr; Costa, P.R.; Griffiths, J.M.; Simon, E.J.; Auger, M.; Halverson, K.J.; Kocisko, D.A.; Hendsch, Z.S.; Ashburn, T.T.; Spencer, R.G.S.; Tidor, B.; Griffin, R.G. Structural model for the β-amyloid fibril based on interstrand alignment of an antiparallel-sheet comprising a C-terminal peptide. Nat. Struct. Biol., 1995, 2(11), 990-998. [http://dx.doi.org/ 10.1038/nsb1195-990]. [PMID: 7583673].
[189]
Petkova, A.T.; Ishii, Y.; Balbach, J.J.; Antzutkin, O.N.; Leapman, R.D.; Delaglio, F.; Tycko, R. A structural model for Alzheimer’s β -amyloid fibrils based on experimental constraints from solid state NMR. Proc. Natl. Acad. Sci. USA, 2002, 99(26), 16742-16747. [http://dx.doi.org/ 10.1073/pnas.262663499]. [PMID: 12481027].
[190]
Pike, C.J.; Burdick, D.; Walencewicz, A.J.; Glabe, C.G.; Cotman, C.W. Neurodegeneration induced by beta-amyloid peptides in vitro: the role of peptide assembly state. J. Neurosci., 1993, 13(4), 1676-1687. [http://dx.doi.org/ 10.1523/JNEUROSCI.13-04-01676.1993]. [PMID: 8463843].
[191]
Pike, C.J.; Walencewicz-Wasserman, A.J.; Kosmoski, J.; Cribbs, D.H.; Glabe, C.G.; Cotman, C.W. Structure-activity analyses of β-amyloid peptides: contributions of the β 25-35 region to aggregation and neurotoxicity. J. Neurochem., 1995, 64(1), 253-265. [http://dx.doi.org/ 10.1046/j.1471-4159.1995.64010253.x]. [PMID: 7798921].
[192]
Lührs, T.; Ritter, C.; Adrian, M.; Riek-Loher, D.; Bohrmann, B.; Döbeli, H.; Schubert, D.; Riek, R. 3D structure of Alzheimer’s amyloid-β(1-42) fibrils. Proc. Natl. Acad. Sci. USA, 2005, 102(48), 17342-17347. [http://dx.doi.org/ 10.1073/pnas.0506723102]. [PMID: 16293696].
[193]
Balducci, C.; Beeg, M.; Stravalaci, M.; Bastone, A.; Sclip, A.; Biasini, E.; Tapella, L.; Colombo, L.; Manzoni, C.; Borsello, T.; Chiesa, R.; Gobbi, M.; Salmona, M.; Forloni, G. Synthetic amyloid-β oligomers impair long-term memory independently of cellular prion protein. Proc. Natl. Acad. Sci. USA, 2010, 107(5), 2295-2300. [http://dx.doi.org/ 10.1073/pnas.0911829107]. [PMID: 20133875].
[194]
Struble, R.G.; Cork, L.C.; Whitehouse, P.J.; Price, D.L. Cholinergic innervation in neuritic plaques. Science, 1982, 216(4544), 413-415. [http://dx.doi.org/ 10.1126/science.6803359]. [PMID: 6803359].
[195]
Morán, M.A.; Mufson, E.J.; Gómez-Ramos, P. Colocalization of cholinesterases with β amyloid protein in aged and Alzheimer’s brains. Acta Neuropathol., 1993, 85(4), 362-369. [http://dx.doi.org/ 10.1007/BF00334445]. [PMID: 8480510].
[196]
Carson, K.A.; Geula, C.; Mesulam, M.M. Electron microscopic localization of cholinesterase activity in Alzheimer brain tissue. Brain Res., 1991, 540(1-2), 204-208. [http://dx.doi.org/ 10.1016/0006-8993(91)90508-S]. [PMID: 2054612].
[197]
Inestrosa, N.C.; Alvarez, A.; Pérez, C.A.; Moreno, R.D.; Vicente, M.; Linker, C.; Casanueva, O.I.; Soto, C.; Garrido, J. Acetylcholinesterase accelerates assembly of amyloid-β-peptides into Alzheimer’s fibrils: Possible role of the peripheral site of the enzyme. Neuron, 1996, 16(4), 881-891. [http://dx.doi.org/ 10.1016/S0896-6273(00)80108-7]. [PMID: 8608006].
[198]
Bartolini, M.; Bertucci, C.; Cavrini, V.; Andrisano, V. β-Amyloid aggregation induced by human acetylcholinesterase: inhibition studies. Biochem. Pharmacol., 2003, 65(3), 407-416. [http://dx.doi.org/10.1016/S0006-2952(02)01514-9]. [PMID: 12527333].
[199]
Lee, G.; Neve, R.L.; Kosik, K.S. The microtubule binding domain of tau protein. Neuron, 1989, 2(6), 1615-1624. [http://dx.doi.org/ 10.1016/0896-6273(89)90050-0]. [PMID: 2516729].
[200]
Binder, L.I.; Frankfurter, A.; Rebhun, L.I. The distribution of tau in the mammalian central nervous system. J. Cell Biol., 1985, 101(4), 1371-1378. [http://dx.doi.org/ 10.1083/jcb.101.4.1371]. [PMID: 3930508].
[201]
Kampers, T.; Pangalos, M.; Geerts, H.; Wiech, H.; Mandelkow, E. Assembly of paired helical filaments from mouse tau: implications for the neurofibrillary pathology in transgenic mouse models for Alzheimer’s disease. FEBS Lett., 1999, 451(1), 39-44. [http://dx.doi.org/ 10.1016/S0014-5793(99)00522-0]. [PMID: 10356980].
[202]
Takashima, A.; Murayama, M.; Murayama, O.; Kohno, T.; Honda, T.; Yasutake, K.; Nihonmatsu, N.; Mercken, M.; Yamaguchi, H.; Sugihara, S.; Wolozin, B. Presenilin 1 associates with glycogen synthase kinase-3β and its substrate tau. Proc. Natl. Acad. Sci. USA, 1998, 95(16), 9637-9641. [http://dx.doi.org/ 10.1073/pnas.95.16.9637]. [PMID: 9689133].
[203]
Mazanetz, M.P.; Fischer, P.M. Untangling tau hyperphosphorylation in drug design for neurodegenerative diseases. Nat. Rev. Drug Discov., 2007, 6(6), 464-479. [http://dx.doi.org/ 10.1038/nrd2111]. [PMID: 17541419].
[204]
Arnold, C.S.; Johnson, G.V.; Cole, R.N.; Dong, D.L-Y.; Lee, M.; Hart, G.W. The microtubule-associated protein tau is extensively modified with O-linked N-acetylglucosamine. J. Biol. Chem., 1996, 271(46), 28741-28744. [http://dx.doi.org/ 10.1074/jbc.271.46. 28741]. [PMID: 8910513].
[205]
Gong, C.X.; Liu, F.; Grundke-Iqbal, I.; Iqbal, K. Post-translational modifications of tau protein in Alzheimer’s disease. J. Neural Transm. (Vienna), 2005, 112(6), 813-838. [http://dx.doi.org/ 10.1007/s00702-004-0221-0]. [PMID: 15517432].
[206]
Lee, V.M.; Balin, B.J.; Otvos, L., Jr; Trojanowski, J.Q. A68: A major subunit of paired helical filaments and derivatized forms of normal Tau. Science, 1991, 251(4994), 675-678. [http://dx.doi.org/ 10.1126/science.1899488]. [PMID: 1899488].
[207]
Schweers, O.; Mandelkow, E-M.; Biernat, J.; Mandelkow, E. Oxidation of cysteine-322 in the repeat domain of microtubule-associated protein tau controls the in vitro assembly of paired helical filaments. Proc. Natl. Acad. Sci. USA, 1995, 92(18), 8463-8467. [http://dx.doi.org/ 10.1073/pnas.92.18.8463]. [PMID: 7667312].
[208]
Ballatore, C.; Lee, V.M.Y.; Trojanowski, J.Q. Tau-mediated neurodegeneration in Alzheimer’s disease and related disorders. Nat. Rev. Neurosci., 2007, 8(9), 663-672. [http://dx.doi.org/ 10.1038/nrn2194]. [PMID: 17684513].
[209]
Novak, M.; Kabat, J.; Wischik, C.M. Molecular characterization of the minimal protease resistant tau unit of the Alzheimer’s disease paired helical filament. EMBO J., 1993, 12(1), 365-370. [http://dx.doi.org/ 10.1002/j.1460-2075.1993.tb05665.x]. [PMID: 7679073].
[210]
von Bergen, M.; Friedhoff, P.; Biernat, J.; Heberle, J.; Mandelkow, E.M.; Mandelkow, E. Assembly of τ protein into Alzheimer paired helical filaments depends on a local sequence motif ((306)VQIVYK(311)) forming β structure. Proc. Natl. Acad. Sci. USA, 2000, 97(10), 5129-5134. [http://dx.doi.org/ 10.1073/pnas.97.10.5129]. [PMID: 10805776].
[211]
Helal, C.J.; Sanner, M.A.; Cooper, C.B.; Gant, T.; Adam, M.; Lucas, J.C.; Kang, Z.; Kupchinsky, S.; Ahlijanian, M.K.; Tate, B.; Menniti, F.S.; Kelly, K.; Peterson, M. Discovery and SAR of 2-aminothiazole inhibitors of cyclin-dependent kinase 5/p25 as a potential treatment for Alzheimer’s disease. Bioorg. Med. Chem. Lett., 2004, 14(22), 5521-5525. [http://dx.doi.org/ 10.1016/j.bmcl.2004.09.006]. [PMID: 15482916].
[212]
Helal, C.J.; Kang, Z.; Lucas, J.C.; Gant, T.; Ahlijanian, M.K.; Schachter, J.B.; Richter, K.E.G.; Cook, J.M.; Menniti, F.S.; Kelly, K.; Mente, S.; Pandit, J.; Hosea, N. Potent and cellularly active 4-aminoimidazole inhibitors of cyclin-dependent kinase 5/p25 for the treatment of Alzheimer’s disease. Bioorg. Med. Chem. Lett., 2009, 19(19), 5703-5707. [http://dx.doi.org/ 10.1016/j.bmcl.2009.08.019]. [PMID: 19700321].
[213]
Chioua, M.; Samadi, A.; Soriano, E.; Lozach, O.; Meijer, L.; Marco-Contelles, J. Synthesis and biological evaluation of 3,6-diamino-1H-pyrazolo[3,4-b]pyridine derivatives as protein kinase inhibitors. Bioorg. Med. Chem. Lett., 2009, 19(16), 4566-4569. [http://dx.doi.org/ 10.1016/j.bmcl.2009.06.099]. [PMID: 19615897].
[214]
Malmström, J.; Viklund, J.; Slivo, C.; Costa, A.; Maudet, M.; Sandelin, C.; Hiller, G.; Olsson, L-L.; Aagaard, A.; Geschwindner, S.; Xue, Y.; Vasänge, M. Synthesis and structure-activity relationship of 4-(1,3-benzothiazol-2-yl)-thiophene-2-sulfonamides as cyclin-dependent kinase 5 (CDK5)/p25 inhibitors. Bioorg. Med. Chem. Lett., 2012, 22(18), 5919-5923. [http://dx.doi.org/ 10.1016/j.bmcl.2012.07.068]. [PMID: 22889803].
[215]
Shiradkar, M.; Thomas, J.; Kanase, V.; Dighe, R. Studying synergism of methyl linked cyclohexyl thiophenes with triazole: synthesis and their CDK5/p25 inhibition activity. Eur. J. Med. Chem., 2011, 46(6), 2066-2074. [http://dx.doi.org/ 10.1016/j.ejmech. 2011.02.059]. [PMID: 21420204].
[216]
Jain, P.; Flaherty, P.T.; Yi, S.; Chopra, I.; Bleasdell, G.; Lipay, J.; Ferandin, Y.; Meijer, L.; Madura, J.D. Design, synthesis, and testing of an 6-O-linked series of benzimidazole based inhibitors of CDK5/p25. Bioorg. Med. Chem., 2011, 19(1), 359-373. [http://dx.doi.org/ 10.1016/j.bmc.2010.11.022]. [PMID: 21144757].
[217]
Chatterjee, A.; Cutler, S.J.; Doerksen, R.J.; Khan, I.A.; Williamson, J.S. Discovery of thienoquinolone derivatives as selective and ATP non-competitive CDK5/p25 inhibitors by structure-based virtual screening. Bioorg. Med. Chem., 2014, 22(22), 6409-6421. [http://dx.doi.org/ 10.1016/j.bmc.2014.09.043]. [PMID: 25438765].
[218]
Dehbi, O.; Tikad, A.; Bourg, S.; Bonnet, P.; Lozach, O.; Meijer, L.; Aadil, M.; Akssira, M.; Guillaumet, G.; Routier, S. Synthesis and optimization of an original V-shaped collection of 4-7-disubstituted pyrido[3,2-d]pyrimidines as CDK5 and DYRK1A inhibitors. Eur. J. Med. Chem., 2014, 80, 352-363. [http://dx.doi.org/ 10.1016/j.ejmech.2014.04.055]. [PMID: 24793883].
[219]
Shiradkar, M.R.; Padhalingappa, M.B.; Bhetalabhotala, S.; Akula, K.C.; Tupe, D.A.; Pinninti, R.R.; Thummanagoti, S. A novel approach to cyclin-dependent kinase 5/p25 inhibitors: A potential treatment for Alzheimer’s disease. Bioorg. Med. Chem., 2007, 15(19), 6397-6406. [http://dx.doi.org/ 10.1016/j.bmc.2007.06.053]. [PMID: 17643991].
[220]
Larsen, S.D.; Stachew, C.F.; Clare, P.M.; Cubbage, J.W.; Leach, K.L. A catch-and-release strategy for the combinatorial synthesis of 4-acylamino-1,3-thiazoles as potential CDK5 inhibitors. Bioorg. Med. Chem. Lett., 2003, 13(20), 3491-3495. [http://dx.doi.org/ 10.1016/S0960-894X(03)00726-1]. [PMID: 14505655].
[221]
Zhong, W.; Liu, H.; Kaller, M.R.; Henley, C.; Magal, E.; Nguyen, T.; Osslund, T.D.; Powers, D.; Rzasa, R.M.; Wang, H-L.; Wang, W.; Xiong, X.; Zhang, J.; Norman, M.H. Design and synthesis of quinolin-2(1H)-one derivatives as potent CDK5 inhibitors. Bioorg. Med. Chem. Lett., 2007, 17(19), 5384-5389. [http://dx.doi.org/ 10.1016/j.bmcl.2007.07.045]. [PMID: 17709247].
[222]
Chen, J.J.; Liu, Q.; Yuan, C.; Gore, V.; Lopez, P.; Ma, V.; Amegadzie, A.; Qian, W.; Judd, T.C.; Minatti, A.E.; Brown, J.; Cheng, Y.; Xue, M.; Zhong, W.; Dineen, T.A.; Epstein, O.; Human, J.; Kreiman, C.; Marx, I.; Weiss, M.M.; Hitchcock, S.A.; Powers, T.S.; Chen, K.; Wen, P.H.; Whittington, D.A.; Cheng, A.C.; Bartberger, M.D.; Hickman, D.; Werner, J.A.; Vargas, H.M.; Everds, N.E.; Vonderfecht, S.L.; Dunn, R.T., II; Wood, S.; Fremeau, R.T., Jr; White, R.D.; Patel, V.F. Development of 2-aminooxazoline 3-azaxanthenes as orally efficacious β-secretase inhibitors for the potential treatment of Alzheimer’s disease. Bioorg. Med. Chem. Lett., 2015, 25(4), 767-774. [http://dx.doi.org/ 10.1016/j.bmcl.2014.12.092]. [PMID: 25613679].
[223]
Hunt, K.W.; Cook, A.W.; Watts, R.J.; Clark, C.T.; Vigers, G.; Smith, D.; Metcalf, A.T.; Gunawardana, I.W.; Burkard, M.; Cox, A.A.; Geck Do, M.K.; Dutcher, D.; Thomas, A.A.; Rana, S.; Kallan, N.C.; DeLisle, R.K.; Rizzi, J.P.; Regal, K.; Sammond, D.; Groneberg, R.; Siu, M.; Purkey, H.; Lyssikatos, J.P.; Marlow, A.; Liu, X.; Tang, T.P. Spirocyclic β-site amyloid precursor protein cleaving enzyme 1 (BACE1) inhibitors: from hit to lowering of cerebrospinal fluid (CSF) amyloid β in a higher species. J. Med. Chem., 2013, 56(8), 3379-3403. [http://dx.doi.org/ 10.1021/jm4002154]. [PMID: 23537249].
[224]
Zou, Y.; Li, L.; Chen, W.; Chen, T.; Ma, L.; Wang, X.; Xiong, B.; Xu, Y.; Shen, J. Virtual screening and structure-based discovery of indole acylguanidines as potent β-secretase (BACE1) inhibitors. Molecules, 2013, 18(5), 5706-5722. [http://dx.doi.org/10.3390/molecules18055706]. [PMID: 23681056].
[225]
Monenschein, H.; Horne, D.B.; Bartberger, M.D.; Hitchcock, S.A.; Nguyen, T.T.; Patel, V.F.; Pennington, L.D.; Zhong, W. Structure guided P1′ modifications of HEA derived β-secretase inhibitors for the treatment of Alzheimer’s disease. Bioorg. Med. Chem. Lett., 2012, 22(11), 3607-3611. [http://dx.doi.org/ 10.1016/j.bmcl.2012.04.060]. [PMID: 22572583].
[226]
Pennington, L.D.; Whittington, D.A.; Bartberger, M.D.; Jordan, S.R.; Monenschein, H.; Nguyen, T.T.; Yang, B.H.; Xue, Q.M.; Vounatsos, F.; Wahl, R.C.; Chen, K.; Wood, S.; Citron, M.; Patel, V.F.; Hitchcock, S.A.; Zhong, W. Hydroxyethylamine-based inhibitors of BACE1: P1–P3 macrocyclization can improve potency, selectivity, and cell activity. Bioorg. Med. Chem. Lett., 2013, 23, 4459-4464. [http://dx.doi.org/10.1016/j.bmcl.2013.05.028]. [PMID: 23769639].
[227]
Rueeger, H.; Lueoend, R.; Rogel, O.; Rondeau, J-M.; Möbitz, H.; Machauer, R.; Jacobson, L.; Staufenbiel, M.; Desrayaud, S.; Neumann, U. Discovery of cyclic sulfone hydroxyethylamines as potent and selective β-site APP-cleaving enzyme 1 (BACE1) inhibitors: Structure-based design and in vivo reduction of amyloid β-peptides. J. Med. Chem., 2012, 55(7), 3364-3386. [http://dx.doi.org/ 10.1021/jm300069y]. [PMID: 22380629].
[228]
Cumming, J.N.; Le, T.X.; Babu, S.; Carroll, C.; Chen, X.; Favreau, L.; Gaspari, P.; Guo, T.; Hobbs, D.W.; Huang, Y.; Iserloh, U.; Kennedy, M.E.; Kuvelkar, R.; Li, G.; Lowrie, J.; McHugh, N.A.; Ozgur, L.; Pan, J.; Parker, E.M.; Saionz, K.; Stamford, A.W.; Strickland, C.; Tadesse, D.; Voigt, J.; Wang, L.; Wu, Y.; Zhang, L.; Zhang, Q. Rational design of novel, potent piperazinone and imidazolidinone BACE1 inhibitors. Bioorg. Med. Chem. Lett., 2008, 18(11), 3236-3241. [http://dx.doi.org/ 10.1016/j.bmcl.2008.04.050]. [PMID: 18468890].
[229]
Cumming, J.; Babu, S.; Huang, Y.; Carrol, C.; Chen, X.; Favreau, L.; Greenlee, W.; Guo, T.; Kennedy, M.; Kuvelkar, R.; Le, T.; Li, G.; McHugh, N.; Orth, P.; Ozgur, L.; Parker, E.; Saionz, K.; Stamford, A.; Strickland, C.; Tadesse, D.; Voigt, J.; Zhang, L.; Zhang, Q. Piperazine sulfonamide BACE1 inhibitors: design, synthesis, and in vivo characterization. Bioorg. Med. Chem. Lett., 2010, 20(9), 2837-2842. [http://dx.doi.org/ 10.1016/j.bmcl.2010.03.050]. [PMID: 20347593].
[230]
Stamford, A.W.; Scott, J.D.; Li, S.W.; Babu, S.; Tadesse, D.; Hunter, R.; Wu, Y.; Misiaszek, J.; Cumming, J.N.; Gilbert, E.J.; Huang, C.; McKittrick, B.A.; Hong, L.; Guo, T.; Zhu, Z.; Strickland, C.; Orth, P.; Voigt, J.H.; Kennedy, M.E.; Chen, X.; Kuvelkar, R.; Hodgson, R.; Hyde, L.A.; Cox, K.; Favreau, L.; Parker, E.M.; Greenlee, W.J. Discovery of an orally available, brain penetrant BACE1 inhibitor that affords robust CNS Aβ reduction. ACS Med. Chem. Lett., 2012, 3(11), 897-902. [http://dx.doi.org/ 10.1021/ml3001165]. [PMID: 23412139].
[231]
Malamas, M.S.; Robichaud, A.; Erdei, J.; Quagliato, D.; Solvibile, W.; Zhou, P.; Morris, K.; Turner, J.; Wagner, E.; Fan, K.; Olland, A.; Jacobsen, S.; Reinhart, P.; Riddell, D.; Pangalos, M. Design and synthesis of aminohydantoins as potent and selective human β-secretase (BACE1) inhibitors with enhanced brain permeability. Bioorg. Med. Chem. Lett., 2010, 20(22), 6597-6605. [http://dx.doi.org/ 10.1016/j.bmcl.2010.09.029]. [PMID: 20880704].
[232]
Kaller, M.R.; Harried, S.S.; Albrecht, B.; Amarante, P.; Babu-Khan, S.; Bartberger, M.D.; Brown, J.; Brown, R.; Chen, K.; Cheng, Y.; Citron, M.; Croghan, M.D.; Graceffa, R.; Hickman, D.; Judd, T.; Kriemen, C.; La, D.; Li, V.; Lopez, P.; Luo, Y.; Masse, C.; Monenschein, H.; Nguyen, T.; Pennington, L.D.; Miguel, T.S.; Sickmier, E.A.; Wahl, R.C.; Weiss, M.M.; Wen, P.H.; Williamson, T.; Wood, S.; Xue, M.; Yang, B.; Zhang, J.; Patel, V.; Zhong, W.; Hitchcock, S. A potent and orally efficacious, hydroxyethylamine-based inhibitor of β-secretase. ACS Med. Chem. Lett., 2012, 3(11), 886-891. [http://dx.doi.org/ 10.1021/ml3000148]. [PMID: 24900403].
[233]
Dineen, T.A.; Weiss, M.M.; Williamson, T.; Acton, P.; Babu-Khan, S.; Bartberger, M.D.; Brown, J.; Chen, K.; Cheng, Y.; Citron, M.; Croghan, M.D.; Dunn, R.T., II; Esmay, J.; Graceffa, R.F.; Harried, S.S.; Hickman, D.; Hitchcock, S.A.; Horne, D.B.; Huang, H.; Imbeah-Ampiah, R.; Judd, T.; Kaller, M.R.; Kreiman, C.R.; La, D.S.; Li, V.; Lopez, P.; Louie, S.; Monenschein, H.; Nguyen, T.T.; Pennington, L.D.; San Miguel, T.; Sickmier, E.A.; Vargas, H.M.; Wahl, R.C.; Wen, P.H.; Whittington, D.A.; Wood, S.; Xue, Q.; Yang, B.H.; Patel, V.F.; Zhong, W. Design and synthesis of potent, orally efficacious hydroxyethylamine derived β-site amyloid precursor protein cleaving enzyme (BACE1) inhibitors. J. Med. Chem., 2012, 55(21), 9025-9044. [http://dx.doi.org/ 10.1021/jm300118s]. [PMID: 22468684].
[234]
May, P.C.; Dean, R.A.; Lowe, S.L.; Martenyi, F.; Sheehan, S.M.; Boggs, L.N.; Monk, S.A.; Mathes, B.M.; Mergott, D.J.; Watson, B.M.; Stout, S.L.; Timm, D.E.; Smith Labell, E.; Gonzales, C.R.; Nakano, M.; Jhee, S.S.; Yen, M.; Ereshefsky, L.; Lindstrom, T.D.; Calligaro, D.O.; Cocke, P.J.; Greg Hall, D.; Friedrich, S.; Citron, M.; Audia, J.E. Robust central reduction of amyloid-β in humans with an orally available, non-peptidic β-secretase inhibitor. J. Neurosci., 2011, 31(46), 16507-16516. [http://dx.doi.org/ 10.1523/JNEUROSCI.3647-11.2011]. [PMID: 22090477].
[235]
Tarazi, H.; Odeh, R.A.; Al-Qawasmeh, R.; Yousef, I.A.; Voelter, W.; Al-Tel, T.H. Design, synthesis and SAR analysis of potent BACE1 inhibitors: Possible lead drug candidates for Alzheimer’s disease. Eur. J. Med. Chem., 2017, 125, 1213-1224. [http://dx.doi.org/10.1016/j.ejmech.2016.11.021]. [PMID: 27871037].
[236]
Azimi, S.; Zonouzi, A.; Firuzi, O.; Iraji, A.; Saeedi, M.; Mahdavi, M.; Edraki, N. Discovery of imidazopyridines containing isoindoline-1,3-dione framework as a new class of BACE1 inhibitors: Design, synthesis and SAR analysis. Eur. J. Med. Chem., 2017, 138, 729-737. [http://dx.doi.org/ 10.1016/j.ejmech.2017.06.040]. [PMID: 28728105].
[237]
Ghosh, A.K.; Brindisi, M.; Yen, Y-C.; Cárdenas, E.L.; Ella-Menye, J-R.; Kumaragurubaran, N.; Huang, X.; Tang, J.; Mesecar, A.D. Design, synthesis, and X-ray structural studies of BACE-1 inhibitors containing substituted 2-oxopiperazines as P1′-P2′ ligands. Bioorg. Med. Chem. Lett., 2017, 27(11), 2432-2438. [http://dx.doi.org/ 10.1016/j.bmcl.2017.04.011]. [PMID: 28427814].
[238]
Bach, A.; Pedersen, T.B.; Strømgaard, K. Design and synthesis of triazole-based peptidomimetics of a PSD-95 PDZ domain inhibitor. MedChemComm, 2016, 7, 531-536. [http://dx.doi.org/ 10.1039/ C5MD00445D].
[239]
Saupe, J.; Roske, Y.; Schillinger, C.; Kamdem, N.; Radetzki, S.; Diehl, A.; Oschkinat, H.; Krause, G.; Heinemann, U.; Rademann, J. Discovery, structure-activity relationship studies, and crystal structure of nonpeptide inhibitors bound to the Shank3 PDZ domain. ChemMedChem, 2011, 6(8), 1411-1422. [http://dx.doi.org/ 10.1002/cmdc.201100094]. [PMID: 21626699].
[240]
Grandy, D.; Shan, J.; Zhang, X.; Rao, S.; Akunuru, S.; Li, H.; Zhang, Y.; Alpatov, I.; Zhang, X.A.; Lang, R.A.; Shi, D-L.; Zheng, J.J. Discovery and characterization of a small molecule inhibitor of the PDZ domain of dishevelled. J. Biol. Chem., 2009, 284(24), 16256-16263. [http://dx.doi.org/10.1074/jbc.M109.009647]. [PMID: 19383605].
[241]
Zhang, W.; Penmatsa, H.; Ren, A.; Punchihewa, C.; Lemoff, A.; Yan, B.; Fujii, N.; Naren, A.P. Functional regulation of cystic fibrosis transmembrane conductance regulator-containing macromolecular complexes: A small-molecule inhibitor approach. Biochem. J., 2011, 435(2), 451-462. [http://dx.doi.org/ 10.1042/BJ20101725]. [PMID: 21299497].
[242]
Bach, A.; Stuhr-Hansen, N.; Thorsen, T.S.; Bork, N.; Moreira, I.S.; Frydenvang, K.; Padrah, S.; Christensen, S.B.; Madsen, K.L.; Weinstein, H.; Gether, U.; Strømgaard, K. Structure-activity relationships of a small-molecule inhibitor of the PDZ domain of PICK1. Org. Biomol. Chem., 2010, 8(19), 4281-4288. [http://dx.doi.org/ 10.1039/c0ob00025f]. [PMID: 20668766].
[243]
Lee, H.J.; Wang, N.X.; Shi, D.L.; Zheng, J.J. Sulindac inhibits canonical Wnt signaling by blocking the PDZ domain of the protein Dishevelled. Angew. Chem. Int. Ed. Engl., 2009, 48(35), 6448-6452. [http://dx.doi.org/ 10.1002/anie.200902981]. [PMID: 19637179].
[244]
Rizzo, S.; Rivière, C.; Piazzi, L.; Bisi, A.; Gobbi, S.; Bartolini, M.; Andrisano, V.; Morroni, F.; Tarozzi, A.; Monti, J-P.; Rampa, A. Benzofuran-based hybrid compounds for the inhibition of cholinesterase activity, β amyloid aggregation, and abeta neurotoxicity. J. Med. Chem., 2008, 51(10), 2883-2886. [http://dx.doi.org/ 10.1021/jm8002747]. [PMID: 18419109].
[245]
Rosini, M.; Simoni, E.; Bartolini, M.; Cavalli, A.; Ceccarini, L.; Pascu, N.; McClymont, D.W.; Tarozzi, A.; Bolognesi, M.L.; Minarini, A.; Tumiatti, V.; Andrisano, V.; Mellor, I.R.; Melchiorre, C. Inhibition of acetylcholinesterase, β-amyloid aggregation, and NMDA receptors in Alzheimer’s disease: a promising direction for the multi-target-directed ligands gold rush. J. Med. Chem., 2008, 51(15), 4381-4384. [http://dx.doi.org/ 10.1021/jm800577j]. [PMID: 18605718].
[246]
Luo, W.; Li, Y.P.; He, Y.; Huang, S.L.; Tan, J.H.; Ou, T.M.; Li, D.; Gu, L.Q.; Huang, Z-S. Design, synthesis and evaluation of novel tacrine-multialkoxybenzene hybrids as dual inhibitors for cholinesterases and amyloid beta aggregation. Bioorg. Med. Chem., 2011, 19(2), 763-770. [http://dx.doi.org/ 10.1016/j.bmc. 2010.12.022]. [PMID: 21211982].
[247]
Yan, J.W.; Li, Y.P.; Ye, W.J.; Chen, S.B.; Hou, J.Q.; Tan, J.H.; Ou, T.M.; Li, D.; Gu, L.Q.; Huang, Z.S. Design, synthesis and evaluation of isaindigotone derivatives as dual inhibitors for acetylcholinesterase and amyloid beta aggregation. Bioorg. Med. Chem., 2012, 20(8), 2527-2534. [http://dx.doi.org/ 10.1016/j.bmc.2012. 02.061]. [PMID: 22444876].
[248]
Shan, W.J.; Huang, L.; Zhou, Q.; Meng, F.C.; Li, X.S. Synthesis, biological evaluation of 9-N-substituted berberine derivatives as multi-functional agents of antioxidant, inhibitors of acetylcholinesterase, butyrylcholinesterase and amyloid-β aggregation. Eur. J. Med. Chem., 2011, 46(12), 5885-5893. [http://dx.doi.org/ 10.1016/j.ejmech.2011.09.051]. [PMID: 22019228].
[249]
Camps, P.; Formosa, X.; Galdeano, C.; Muñoz-Torrero, D.; Ramírez, L.; Gómez, E.; Isambert, N.; Lavilla, R.; Badia, A.; Clos, M.V.; Bartolini, M.; Mancini, F.; Andrisano, V.; Arce, M.P.; Rodríguez-Franco, M.I.; Huertas, O.; Dafni, T.; Luque, F.J. Pyrano[3,2-c]quinoline-6-chlorotacrine hybrids as a novel family of acetylcholinesterase- and β-amyloid-directed anti-Alzheimer compounds. J. Med. Chem., 2009, 52(17), 5365-5379. [http://dx.doi.org/ 10.1021/jm900859q]. [PMID: 19663388].
[250]
Shi, A.; Huang, L.; Lu, C.; He, F.; Li, X. Synthesis, biological evaluation and molecular modeling of novel triazole-containing berberine derivatives as acetylcholinesterase and β-amyloid aggregation inhibitors. Bioorg. Med. Chem., 2011, 19(7), 2298-2305. [http://dx.doi.org/ 10.1016/j.bmc.2011.02.025]. [PMID: 21397508].
[251]
Tang, H.; Zhao, L.Z.; Zhao, H.T.; Huang, S.L.; Zhong, S.M.; Qin, J.K.; Chen, Z.F.; Huang, Z.S.; Liang, H. Hybrids of oxoisoaporphine-tacrine congeners: novel acetylcholinesterase and acetylcholinesterase-induced β-amyloid aggregation inhibitors. Eur. J. Med. Chem., 2011, 46(10), 4970-4979. [http://dx.doi.org/10.1016/j.ejmech.2011.08.002]. [PMID: 21871694].
[252]
Tumiatti, V.; Milelli, A.; Minarini, A.; Rosini, M.; Bolognesi, M.L.; Micco, M.; Andrisano, V.; Bartolini, M.; Mancini, F.; Recanatini, M.; Cavalli, A.; Melchiorre, C. Structure-activity relationships of acetylcholinesterase noncovalent inhibitors based on a polyamine backbone. 4. Further investigation on the inner spacer. J. Med. Chem., 2008, 51(22), 7308-7312. [http://dx.doi.org/ 10.1021/jm8009684]. [PMID: 18954037].
[253]
Chen, X.; Wehle, S.; Kuzmanovic, N.; Merget, B.; Holzgrabe, U.; König, B. Acetylcholinesterase inhibitors with photoswitchable inhibition of β-amyloid aggregation. ACS Chem. Neurosci., 2014, 5, 377-389.
[254]
Tang, H.; Zhao, H.T.; Zhong, S.M.; Wang, Z.Y.; Chen, Z.F.; Liang, H. Novel oxoisoaporphine-based inhibitors of acetyl- and butyrylcholinesterase and acetylcholinesterase-induced beta-amyloid aggregation. Bioorg. Med. Chem. Lett., 2012, 22(6), 2257-2261. [http://dx.doi.org/ 10.1016/j.bmcl.2012.01.090]. [PMID: 22341944].
[255]
Belluti, F.; Bartolini, M.; Bottegoni, G.; Bisi, A.; Cavalli, A.; Andrisano, V.; Rampa, A. Benzophenone-based derivatives: a novel series of potent and selective dual inhibitors of acetylcholinesterase and acetylcholinesterase-induced beta-amyloid aggregation. Eur. J. Med. Chem., 2011, 46(5), 1682-1693. [http://dx.doi.org/ 10.1016/j.ejmech.2011.02.019]. [PMID: 21397996].
[256]
Nepovimova, E.; Uliassi, E.; Korabecny, J.; Peña-Altamira, L.E.; Samez, S.; Pesaresi, A.; Garcia, G.E.; Bartolini, M.; Andrisano, V.; Bergamini, C.; Fato, R.; Lamba, D.; Roberti, M.; Kuca, K.; Monti, B.; Bolognesi, M.L. Multitarget drug design strategy: quinone-tacrine hybrids designed to block amyloid-β aggregation and to exert anticholinesterase and antioxidant effects. J. Med. Chem., 2014, 57(20), 8576-8589. [http://dx.doi.org/ 10.1021/jm5010804]. [PMID: 25259726].
[257]
Huang, L.; Lu, C.; Sun, Y.; Mao, F.; Luo, Z.; Su, T.; Jiang, H.; Shan, W.; Li, X. Multitarget-directed benzylideneindanone derivatives: anti-β-amyloid (Aβ) aggregation, antioxidant, metal chelation, and monoamine oxidase B (MAO-B) inhibition properties against Alzheimer’s disease. J. Med. Chem., 2012, 55(19), 8483-8492. [http://dx.doi.org/ 10.1021/jm300978h]. [PMID: 22978824].
[258]
Soto-Ortega, D.D.; Murphy, B.P.; Gonzalez-Velasquez, F.J.; Wilson, K.A.; Xie, F.; Wang, Q.; Moss, M.A. Inhibition of amyloid-β aggregation by coumarin analogs can be manipulated by functionalization of the aromatic center. Bioorg. Med. Chem., 2011, 19(8), 2596-2602. [http://dx.doi.org/ 10.1016/j.bmc.2011.03.010]. [PMID: 21458277].
[259]
Alptüzün, V.; Prinz, M.; Hörr, V.; Scheiber, J.; Radacki, K.; Fallarero, A.; Vuorela, P.; Engels, B.; Braunschweig, H.; Erciyas, E.; Holzgrabe, U. Interaction of (benzylidene-hydrazono)-1,4-dihydropyridines with β-amyloid, acetylcholine, and butyrylcholine esterases. Bioorg. Med. Chem., 2010, 18(5), 2049-2059. [http://dx.doi.org/ 10.1016/j.bmc.2010.01.002]. [PMID: 20149667].
[260]
Aydın, A.; Akkurt, M.; Alptüzün, V.; Büyükgüngör, O.; Holzgrabe, U.; Radacki, K. 4-[(2E)-2-(4-Chloro-benzyl-idene)hydrazinyl-idene]-1-methyl-1,4-dihydro-pyridine monohydrate. Acta Crystallogr. Sect. E Struct. Rep., 2010, 66(Pt 6), 1324-1325. [http://dx.doi.org/10.1107/S1600536810015709]. [PMID: 21579416].
[261]
Prinz, M.; Parlar, S.; Bayraktar, G.; Alptüzün, V.; Erciyas, E.; Fallarero, A.; Karlsson, D.; Vuorela, P.; Burek, M.; Förster, C.; Turunc, E.; Armagan, G.; Yalcin, A.; Schiller, C.; Leuner, K.; Krug, M.; Sotriffer, C.A.; Holzgrabe, U. 1,4-Substituted 4-(1H)-pyridylene-hydrazone-type inhibitors of AChE, BuChE, and amyloid-β aggregation crossing the blood-brain barrier. Eur. J. Pharm. Sci., 2013, 49(4), 603-613. [http://dx.doi.org/ 10.1016/j.ejps.2013.04.024]. [PMID: 23643737].
[262]
Panek, D.; Więckowska, A.; Wichur, T.; Bajda, M.; Godyń, J.; Jończyk, J.; Mika, K.; Janockova, J.; Soukup, O.; Knez, D.; Korabecny, J.; Gobec, S.; Malawska, B. Design, synthesis and biological evaluation of new phthalimide and saccharin derivatives with alicyclic amines targeting cholinesterases, beta-secretase and amyloid beta aggregation. Eur. J. Med. Chem., 2017, 125, 676-695. [http://dx.doi.org/10.1016/j.ejmech.2016.09.078]. [PMID: 27721153].
[263]
Więckowska, A.; Więckowski, K.; Bajda, M.; Brus, B.; Sałat, K.; Czerwińska, P.; Gobec, S.; Filipek, B.; Malawska, B. Synthesis of new N-benzylpiperidine derivatives as cholinesterase inhibitors with β-amyloid anti-aggregation properties and beneficial effects on memory in vivo. Bioorg. Med. Chem., 2015, 23(10), 2445-2457. [http://dx.doi.org/ 10.1016/j.bmc.2015.03.051]. [PMID: 25868744].
[264]
Guzior, N.; Bajda, M.; Skrok, M.; Kurpiewska, K.; Lewiński, K.; Brus, B.; Pišlar, A.; Kos, J.; Gobec, S.; Malawska, B. Development of multifunctional, heterodimeric isoindoline-1,3-dione derivatives as cholinesterase and β-amyloid aggregation inhibitors with neuroprotective properties. Eur. J. Med. Chem., 2015, 92, 738-749. [http://dx.doi.org/10.1016/j.ejmech.2015.01.027]. [PMID: 25621991].
[265]
Zha, G.F.; Zhang, C.P.; Qin, H.L.; Jantan, I.; Sher, M.; Amjad, M.W.; Hussain, M.A.; Hussain, Z.; Bukhari, S.N.A. Biological evaluation of synthetic α,β-unsaturated carbonyl based cyclohexanone derivatives as neuroprotective novel inhibitors of acetylcholinesterase, butyrylcholinesterase and amyloid-β aggregation. Bioorg. Med. Chem., 2016, 24(10), 2352-2359. [http://dx.doi.org/ 10.1016/j.bmc.2016.04.015]. [PMID: 27083471].
[266]
Sun, Q.; Peng, D.Y.; Yang, S.G.; Zhu, X.L.; Yang, W.C.; Yang, G.F. Syntheses of coumarin-tacrine hybrids as dual-site acetylcholinesterase inhibitors and their activity against butylcholinesterase, Aβ aggregation, and β-secretase. Bioorg. Med. Chem., 2014, 22(17), 4784-4791. [http://dx.doi.org/ 10.1016/j.bmc.2014.06.057]. [PMID: 25088549].
[267]
Vyas, N.A.; Bhat, S.S.; Kumbhar, A.S.; Sonawane, U.B.; Jani, V.; Joshi, R.R.; Ramteke, S.N.; Kulkarni, P.P.; Joshi, B. Ruthenium(II) polypyridyl complex as inhibitor of acetylcholinesterase and Aβ aggregation. Eur. J. Med. Chem., 2014, 75, 375-381. [http://dx.doi.org/10.1016/j.ejmech.2014.01.052]. [PMID: 24556150].
[268]
Viayna, E.; Sola, I.; Bartolini, M.; De Simone, A.; Tapia-Rojas, C.; Serrano, F.G.; Sabaté, R.; Juárez-Jiménez, J.; Pérez, B.; Luque, F.J.; Andrisano, V.; Clos, M.V.; Inestrosa, N.C.; Muñoz-Torrero, D. Synthesis and multitarget biological profiling of a novel family of rhein derivatives as disease-modifying anti-Alzheimer agents. J. Med. Chem., 2014, 57(6), 2549-2567. [http://dx.doi.org/ 10.1021/jm401824w]. [PMID: 24568372].
[269]
Lemes, L.F.N.; de Andrade Ramos, G.; de Oliveira, A.S.; da Silva, F.M.R.; de Castro Couto, G.; da Silva Boni, M.; Guimarães, M.J.R.; Souza, I.N.O.; Bartolini, M.; Andrisano, V.; do Nascimento Nogueira, P.C.; Silveira, E.R.; Brand, G.D.; Soukup, O.; Korábečný, J.; Romeiro, N.C.; Castro, N.G.; Bolognesi, M.L.; Romeiro, L.A.S. Cardanol-derived AChE inhibitors: Towards the development of dual binding derivatives for Alzheimer’s disease. Eur. J. Med. Chem., 2016, 108, 687-700. [http://dx.doi.org/ 10.1016/j.ejmech.2015.12.024]. [PMID: 26735910].
[270]
Brogi, S.; Butini, S.; Maramai, S.; Colombo, R.; Verga, L.; Lanni, C.; De Lorenzi, E.; Lamponi, S.; Andreassi, M.; Bartolini, M.; Andrisano, V.; Novellino, E.; Campiani, G.; Brindisi, M.; Gemma, S. Disease-modifying anti-Alzheimer’s drugs: inhibitors of human cholinesterases interfering with β-amyloid aggregation. CNS Neurosci. Ther., 2014, 20(7), 624-632. [http://dx.doi.org/ 10.1111/cns.12290]. [PMID: 24935788].
[271]
Mishra, C.B.; Kumari, S.; Manral, A.; Prakash, A.; Saini, V.; Lynn, A.M.; Tiwari, M. Design, synthesis, in-silico and biological evaluation of novel donepezil derivatives as multi-target-directed ligands for the treatment of Alzheimer’s disease. Eur. J. Med. Chem., 2017, 125, 736-750. [http://dx.doi.org/ 10.1016/j.ejmech.2016.09.057]. [PMID: 27721157].
[272]
Luo, W.; Wang, T.; Hong, C.; Yang, Y.C.; Chen, Y.; Cen, J.; Xie, S.Q.; Wang, C.J. Design, synthesis and evaluation of 4-dimethylamine flavonoid derivatives as potential multifunctional anti-Alzheimer agents. Eur. J. Med. Chem., 2016, 122, 17-26. [http://dx.doi.org/10.1016/j.ejmech.2016.06.022]. [PMID: 27343850].
[273]
Panek, D.; Więckowska, A.; Jończyk, J.; Godyń, J.; Bajda, M.; Wichur, T.; Pasieka, A.; Knez, D.; Pišlar, A.; Korabecny, J.; Soukup, O.; Sepsova, V.; Sabaté, R.; Kos, J.; Gobec, S.; Malawska, B. Design, synthesis, and biological evaluation of 1-benzylamino-2-hydroxyalkyl derivatives as new potential disease-modifying multifunctional anti-Alzheimer’s agents. ACS Chem. Neurosci., 2018, 9(5), 1074-1094. [http://dx.doi.org/ 10.1021/acschemneuro. 7b00461]. [PMID: 29345897].
[274]
Chen, K-L.; Gan, L.; Wu, Z-H.; Qin, J-F.; Liao, W-X.; Tang, H. 4- Substituted sampangine derivatives: Novel acetylcholinesterase and β-myloid aggregation inhibitors. Int. J. Biol. Macromol., 2018, 107, (Pt B), 2725-2729. [http://dx.doi.org/ 10.1016/j.ijbiomac.2017.10.157]. [PMID: 29111270].
[275]
Kumar, D.; Gupta, S.K.; Ganeshpurkar, A.; Gutti, G.; Krishnamurthy, S.; Modi, G.; Singh, S.K. Development of piperazinediones as dual inhibitor for treatment of Alzheimer’s disease. Eur. J. Med. Chem., 2018, 150, 87-101. [http://dx.doi.org/ 10.1016/j. ejmech.2018.02.078]. [PMID: 29524731].
[276]
Bulic, B.; Pickhardt, M.; Khlistunova, I.; Biernat, J.; Mandelkow, E.M.; Mandelkow, E.; Waldmann, H. Rhodanine-based tau aggregation inhibitors in cell models of tauopathy. Angew. Chem. Int. Ed. Engl., 2007, 46(48), 9215-9219. [http://dx.doi.org/ 10.1002/anie.200704051]. [PMID: 17985339].
[277]
Larbig, G.; Pickhardt, M.; Lloyd, D.G.; Schmidt, B.; Mandelkow, E. Screening for inhibitors of tau protein aggregation into Alzheimer paired helical filaments: a ligand based approach results in successful scaffold hopping. Curr. Alzheimer Res., 2007, 4(3), 315-323. [http://dx.doi.org/ 10.2174/156720507781077250]. [PMID: 17627489].
[278]
Pickhardt, M.; Larbig, G.; Khlistunova, I.; Coksezen, A.; Meyer, B.; Mandelkow, E-M.; Schmidt, B.; Mandelkow, E. Phenylthiazolyl-hydrazide and its derivatives are potent inhibitors of τ aggregation and toxicity in vitro and in cells. Biochemistry, 2007, 46(35), 10016-10023. [http://dx.doi.org/ 10.1021/bi700878g]. [PMID: 17685560].
[279]
Pickhardt, M.; Gazova, Z.; von Bergen, M.; Khlistunova, I.; Wang, Y.; Hascher, A.; Mandelkow, E-M.; Biernat, J.; Mandelkow, E. Anthraquinones inhibit tau aggregation and dissolve Alzheimer’s paired helical filaments in vitro and in cells. J. Biol. Chem., 2005, 280(5), 3628-3635. [http://dx.doi.org/ 10.1074/jbc.M410984200]. [PMID: 15525637].
[280]
Necula, M.; Chirita, C.N.; Kuret, J. Cyanine dye N744 inhibits tau fibrillization by blocking filament extension: Implications for the treatment of tauopathic neurodegenerative diseases. Biochemistry, 2005, 44(30), 10227-10237. [http://dx.doi.org/ 10.1021/bi050387o]. [PMID: 16042400].
[281]
Hattori, M.; Sugino, E.; Minoura, K.; In, Y.; Sumida, M.; Taniguchi, T.; Tomoo, K.; Ishida, T. Different inhibitory response of cyanidin and methylene blue for filament formation of tau microtubule-binding domain. Biochem. Biophys. Res. Commun., 2008, 374(1), 158-163. [http://dx.doi.org/ 10.1016/j.bbrc.2008.07.001]. [PMID: 18619417].
[282]
Taniguchi, S.; Suzuki, N.; Masuda, M.; Hisanaga, S.; Iwatsubo, T.; Goedert, M.; Hasegawa, M. Inhibition of heparin-induced tau filament formation by phenothiazines, polyphenols, and porphyrins. J. Biol. Chem., 2005, 280(9), 7614-7623. [http://dx.doi.org/ 10.1074/jbc.M408714200]. [PMID: 15611092].
[283]
Crowe, A.; Ballatore, C.; Hyde, E.; Trojanowski, J.Q.; Lee, V.M.Y. High throughput screening for small molecule inhibitors of heparin-induced tau fibril formation. Biochem. Biophys. Res. Commun., 2007, 358(1), 1-6. [http://dx.doi.org/ 10.1016/j.bbrc.2007.03.056]. [PMID: 17482143].
[284]
Honson, N.S.; Jensen, J.R.; Darby, M.V.; Kuret, J. Potent inhibition of tau fibrillization with a multivalent ligand. Biochem. Biophys. Res. Commun., 2007, 363(1), 229-234. [http://dx.doi.org/ 10.1016/j.bbrc.2007.08.166]. [PMID: 17854770].
[285]
Daccache, A.; Lion, C.; Sibille, N.; Gerard, M.; Slomianny, C.; Lippens, G.; Cotelle, P. Oleuropein and derivatives from olives as Tau aggregation inhibitors. Neurochem. Int., 2011, 58(6), 700-707. [http://dx.doi.org/ 10.1016/j.neuint.2011.02.010]. [PMID: 21333710].


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 19
ISSUE: 7
Year: 2019
Page: [501 - 533]
Pages: 33
DOI: 10.2174/1568026619666190304153353
Price: $58

Article Metrics

PDF: 30
HTML: 3