Generic placeholder image

Current Topics in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1568-0266
ISSN (Online): 1873-4294

Review Article

Targeting Tau Hyperphosphorylation via Kinase Inhibition: Strategy to Address Alzheimer's Disease

Author(s): Ahmad Abu Turab Naqvi, Gulam Mustafa Hasan and Md. Imtaiyaz Hassan*

Volume 20, Issue 12, 2020

Page: [1059 - 1073] Pages: 15

DOI: 10.2174/1568026620666200106125910

Price: $65

Abstract

Microtubule-associated protein tau is involved in the tubulin binding leading to microtubule stabilization in neuronal cells which is essential for stabilization of neuron cytoskeleton. The regulation of tau activity is accommodated by several kinases which phosphorylate tau protein on specific sites. In pathological conditions, abnormal activity of tau kinases such as glycogen synthase kinase-3 β (GSK3β), cyclin-dependent kinase 5 (CDK5), c-Jun N-terminal kinases (JNKs), extracellular signal-regulated kinase 1 and 2 (ERK1/2) and microtubule affinity regulating kinase (MARK) lead to tau hyperphosphorylation. Hyperphosphorylation of tau protein leads to aggregation of tau into paired helical filaments like structures which are major constituents of neurofibrillary tangles, a hallmark of Alzheimer’s disease. In this review, we discuss various tau protein kinases and their association with tau hyperphosphorylation. We also discuss various strategies and the advancements made in the area of Alzheimer's disease drug development by designing effective and specific inhibitors for such kinases using traditional in vitro/in vivo methods and state of the art in silico techniques.

Keywords: Alzheimer's disease, Neurodegenerative diseases, Tau hyperphosphorylation, Tau kinases, Kinase Inhibitors, Drug discovery.

Graphical Abstract
[1]
Schachter, A.S.; Davis, K.L. Alzheimer’s disease. Dialogues Clin. Neurosci., 2000, 2(2), 91-100.
[PMID: 22034442]
[2]
De-Paula, V.J.; Radanovic, M.; Diniz, B.S.; Forlenza, O.V. Alzheimer’s disease. Subcell. Biochem., 2012, 65, 329-352.
[http://dx.doi.org/10.1007/978-94-007-5416-4_14] [PMID: 23225010]
[3]
Armstrong, R.A. What causes alzheimer’s disease? Folia Neuropathol., 2013, 51(3), 169-188.
[http://dx.doi.org/10.5114/fn.2013.37702] [PMID: 24114635]
[4]
Gong, C.X.; Iqbal, K. Hyperphosphorylation of microtubule-associated protein tau: a promising therapeutic target for Alzheimer disease. Curr. Med. Chem., 2008, 15(23), 2321-2328.
[http://dx.doi.org/10.2174/092986708785909111] [PMID: 18855662]
[5]
Dolan, P.J.; Johnson, G.V. The role of tau kinases in Alzheimer’s disease. Curr. Opin. Drug Discov. Devel., 2010, 13(5), 595-603.
[PMID: 20812151]
[6]
Martin, L.; Latypova, X.; Wilson, C.M.; Magnaudeix, A.; Perrin, M.L.; Yardin, C.; Terro, F. Tau protein kinases: involvement in Alzheimer’s disease. Ageing Res. Rev., 2013, 12(1), 289-309.
[http://dx.doi.org/10.1016/j.arr.2012.06.003] [PMID: 22742992]
[7]
Buée, L.; Bussière, T.; Buée-Scherrer, V.; Delacourte, A.; Hof, P.R. Tau protein isoforms, phosphorylation and role in neurodegenerative disorders. Brain Res. Brain Res. Rev., 2000, 33(1), 95-130.
[http://dx.doi.org/10.1016/S0165-0173(00)00019-9] [PMID: 10967355]
[8]
Kolarova, M.; García-Sierra, F.; Bartos, A.; Ricny, J.; Ripova, D. Structure and pathology of tau protein in Alzheimer disease. Int. J. Alzheimers Dis., 2012, 2012 731526
[http://dx.doi.org/10.1155/2012/731526] [PMID: 22690349]
[9]
Wang, J.Z.; Xia, Y.Y.; Grundke-Iqbal, I.; Iqbal, K. Abnormal hyperphosphorylation of tau: sites, regulation, and molecular mechanism of neurofibrillary degeneration. J. Alzheimers Dis., 2013, 33(Suppl. 1), S123-S139.
[http://dx.doi.org/10.3233/JAD-2012-129031] [PMID: 22710920]
[10]
Šimić, G.; Babić Leko, M.; Wray, S.; Harrington, C.; Delalle, I.; Jovanov-Milošević, N.; Bažadona, D.; Buée, L.; de Silva, R.; Di Giovanni, G.; Wischik, C.; Hof, P.R. Tau protein hyperphosphorylation and aggregation in alzheimer’s disease and other tauopathies, and possible neuroprotective strategies. Biomolecules, 2016, 6(1), 6.
[http://dx.doi.org/10.3390/biom6010006] [PMID: 26751493]
[11]
Kozlov, S.; Afonin, A.; Evsyukov, I.; Bondarenko, A. Alzheimer’s disease: as it was in the beginning. Rev. Neurosci., 2017, 28(8), 825-843.
[http://dx.doi.org/10.1515/revneuro-2017-0006] [PMID: 28704198]
[12]
Blennow, K.; de Leon, M.J.; Zetterberg, H. Alzheimer’s disease. Lancet, 2006, 368(9533), 387-403.
[http://dx.doi.org/10.1016/S0140-6736(06)69113-7] [PMID: 16876668]
[13]
Iqbal, K.; Liu, F.; Gong, C.X.; Grundke-Iqbal, I. Tau in Alzheimer disease and related tauopathies. Curr. Alzheimer Res., 2010, 7(8), 656-664.
[http://dx.doi.org/10.2174/156720510793611592] [PMID: 20678074]
[14]
Gao, Y.; Tan, L.; Yu, J.T.; Tan, L. Tau in alzheimer’s disease: Mechanisms and therapeutic strategies. Curr. Alzheimer Res., 2018, 15(3), 283-300.
[http://dx.doi.org/10.2174/1567205014666170417111859] [PMID: 28413986]
[15]
Scheltens, P.; Blennow, K.; Breteler, M.M.; de Strooper, B.; Frisoni, G.B.; Salloway, S.; Van der Flier, W.M. Alzheimer’s disease. Lancet, 2016, 388(10043), 505-517.
[http://dx.doi.org/10.1016/S0140-6736(15)01124-1] [PMID: 26921134]
[16]
Mandelkow, E-M.; Mandelkow, E. Tau in Alzheimer’s disease. Trends Cell Biol., 1998, 8(11), 425-427.
[http://dx.doi.org/10.1016/S0962-8924(98)01368-3] [PMID: 9854307]
[17]
Liu, F.; Li, B.; Tung, E.J.; Grundke-Iqbal, I.; Iqbal, K.; Gong, C.X. Site-specific effects of tau phosphorylation on its microtubule assembly activity and self-aggregation. Eur. J. Neurosci., 2007, 26(12), 3429-3436.
[http://dx.doi.org/10.1111/j.1460-9568.2007.05955.x] [PMID: 18052981]
[18]
Serrano-Pozo, A.; Frosch, M.P.; Masliah, E.; Hyman, B.T. Neuropathological alterations in Alzheimer disease. Cold Spring Harb. Perspect. Med., 2011, 1(1) a006189
[http://dx.doi.org/10.1101/cshperspect.a006189] [PMID: 22229116]
[19]
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]
[20]
Cho, J.H.; Johnson, G.V. Primed phosphorylation of tau at Thr231 by glycogen synthase kinase 3beta (GSK3beta) plays a critical role in regulating tau’s ability to bind and stabilize microtubules. J. Neurochem., 2004, 88(2), 349-358.
[http://dx.doi.org/10.1111/j.1471-4159.2004.02155.x] [PMID: 14690523]
[21]
Choi, S.H.; Kim, Y.H.; Hebisch, M.; Sliwinski, C.; Lee, S.; D’Avanzo, C.; Chen, H.; Hooli, B.; Asselin, C.; Muffat, J.; Klee, J.B.; Zhang, C.; Wainger, B.J.; Peitz, M.; Kovacs, D.M.; Woolf, C.J.; Wagner, S.L.; Tanzi, R.E.; Kim, D.Y. A three-dimensional human neural cell culture model of Alzheimer’s disease. Nature, 2014, 515(7526), 274-278.
[http://dx.doi.org/10.1038/nature13800] [PMID: 25307057]
[22]
Kimura, T.; Ishiguro, K.; Hisanaga, S. Physiological and pathological phosphorylation of tau by Cdk5. Front. Mol. Neurosci., 2014, 7, 65.
[http://dx.doi.org/10.3389/fnmol.2014.00065] [PMID: 25076872]
[23]
Sun, L.H.; Ban, T.; Liu, C.D.; Chen, Q.X.; Wang, X.; Yan, M.L.; Hu, X.L.; Su, X.L.; Bao, Y.N.; Sun, L.L.; Zhao, L.J.; Pei, S.C.; Jiang, X.M.; Zong, D.K.; Ai, J. Activation of Cdk5/p25 and tau phosphorylation following chronic brain hypoperfusion in rats involves microRNA-195 down-regulation. J. Neurochem., 2015, 134(6), 1139-1151.
[http://dx.doi.org/10.1111/jnc.13212] [PMID: 26118667]
[24]
Mebratu, Y.; Tesfaigzi, Y. How ERK1/2 activation controls cell proliferation and cell death: Is subcellular localization the answer? Cell Cycle, 2009, 8(8), 1168-1175.
[http://dx.doi.org/10.4161/cc.8.8.8147] [PMID: 19282669]
[25]
Sergeant, N.; Bretteville, A.; Hamdane, M.; Caillet-Boudin, M.L.; Grognet, P.; Bombois, S.; Blum, D.; Delacourte, A.; Pasquier, F.; Vanmechelen, E.; Schraen-Maschke, S.; Buée, L. Biochemistry of Tau in Alzheimer’s disease and related neurological disorders. Expert Rev. Proteomics, 2008, 5(2), 207-224.
[http://dx.doi.org/10.1586/14789450.5.2.207] [PMID: 18466052]
[26]
Feijoo, C.; Campbell, D.G.; Jakes, R.; Goedert, M.; Cuenda, A. Evidence that phosphorylation of the microtubule-associated protein Tau by SAPK4/p38delta at Thr50 promotes microtubule assembly. J. Cell Sci., 2005, 118(Pt 2), 397-408.
[http://dx.doi.org/10.1242/jcs.01655] [PMID: 15632108]
[27]
Zhu, X.; Rottkamp, C.A.; Boux, H.; Takeda, A.; Perry, G.; Smith, M.A. Activation of p38 kinase links tau phosphorylation, oxidative stress, and cell cycle-related events in Alzheimer disease. J. Neuropathol. Exp. Neurol., 2000, 59(10), 880-888.
[http://dx.doi.org/10.1093/jnen/59.10.880] [PMID: 11079778]
[28]
Ploia, C.; Antoniou, X.; Sclip, A.; Grande, V.; Cardinetti, D.; Colombo, A.; Canu, N.; Benussi, L.; Ghidoni, R.; Forloni, G.; Borsello, T. JNK plays a key role in tau hyperphosphorylation in Alzheimer’s disease models. J. Alzheimers Dis., 2011, 26(2), 315-329.
[http://dx.doi.org/10.3233/JAD-2011-110320] [PMID: 21628793]
[29]
Alavi Naini, S.M.; Soussi-Yanicostas, N. Tau hyperphosphorylation and oxidative stress, a critical vicious circle in neurodegenerative tauopathies? Oxid. Med. Cell. Longev., 2015, 2015 151979
[http://dx.doi.org/10.1155/2015/151979] [PMID: 26576216]
[30]
Naz, F.; Anjum, F.; Islam, A.; Ahmad, F.; Hassan, M.I. Microtubule affinity-regulating kinase 4: structure, function, and regulation. Cell Biochem. Biophys., 2013, 67(2), 485-499.
[http://dx.doi.org/10.1007/s12013-013-9550-7] [PMID: 23471664]
[31]
Naz, H.; Islam, A.; Ahmad, F.; Hassan, M.I. Calcium/calmodulin-dependent protein kinase IV: A multifunctional enzyme and potential therapeutic target. Prog. Biophys. Mol. Biol., 2016, 121(1), 54-65.
[http://dx.doi.org/10.1016/j.pbiomolbio.2015.12.016] [PMID: 26773169]
[32]
Tang, E.I.; Mruk, D.D.; Cheng, C.Y. MAP/microtubule affinity-regulating kinases, microtubule dynamics, and spermatogenesis. J. Endocrinol., 2013, 217(2), R13-R23.
[http://dx.doi.org/10.1530/JOE-12-0586] [PMID: 23449618]
[33]
Gu, G.J.; Lund, H.; Wu, D.; Blokzijl, A.; Classon, C.; von Euler, G.; Landegren, U.; Sunnemark, D.; Kamali-Moghaddam, M. Role of individual mark isoforms in phosphorylation of tau at ser(2)(6)(2) in alzheimer’s disease. Neuromolecular Med., 2013, 15(3), 458-469.
[http://dx.doi.org/10.1007/s12017-013-8232-3] [PMID: 23666762]
[34]
Annadurai, N.; Agrawal, K.; Džubák, P.; Hajdúch, M.; Das, V. Microtubule affinity-regulating kinases are potential druggable targets for Alzheimer’s disease. Cell. Mol. Life Sci., 2017, 74(22), 4159-4169.
[http://dx.doi.org/10.1007/s00018-017-2574-1] [PMID: 28634681]
[35]
Khan, P.; Queen, A.; Mohammad, T.; Smita, ; Khan, N.S.; Hafeez, Z.B.; Hassan, M.I.; Ali, S.; Smita, Khan, N.S.; Hafeez, Z.B.; Hassan, M.I.; Ali, S. Identification of alpha-mangostin as a potential inhibitor of microtubule affinity regulating kinase 4. J. Nat. Prod., 2019, 82(8), 2252-2261.
[http://dx.doi.org/10.1021/acs.jnatprod.9b00372] [PMID: 31343173]
[36]
Mohammad, T.; Khan, F.I.; Lobb, K.A.; Islam, A.; Ahmad, F.; Hassan, M.I. Identification and evaluation of bioactive natural products as potential inhibitors of human microtubule affinity-regulating kinase 4 (MARK4). J. Biomol. Struct. Dyn., 2019, 37(7), 1813-1829.
[http://dx.doi.org/10.1080/07391102.2018.1468282] [PMID: 29683402]
[37]
Liao, J.C.; Yang, T.T.; Weng, R.R.; Kuo, C.T.; Chang, C.W. TTBK2: a tau protein kinase beyond tau phosphorylation. BioMed Res. Int., 2015, 2015 575170
[http://dx.doi.org/10.1155/2015/575170] [PMID: 25950000]
[38]
Xu, J.; Sato, S.; Okuyama, S.; Swan, R.J.; Jacobsen, M.T.; Strunk, E.; Ikezu, T. Tau-tubulin kinase 1 enhances prefibrillar tau aggregation and motor neuron degeneration in P301L FTDP-17 tau-mutant mice. FASEB J., 2010, 24(8), 2904-2915.
[http://dx.doi.org/10.1096/fj.09-150144] [PMID: 20354135]
[39]
Nozal, V.; Martinez, A. Tau Tubulin Kinase 1 (TTBK1), a new player in the fight against neurodegenerative diseases. Eur. J. Med. Chem., 2019, 161, 39-47.
[http://dx.doi.org/10.1016/j.ejmech.2018.10.030] [PMID: 30342424]
[40]
Bahassi, E.M.; Ovesen, J.L.; Riesenberg, A.L.; Bernstein, W.Z.; Hasty, P.E.; Stambrook, P.J. The checkpoint kinases Chk1 and Chk2 regulate the functional associations between hBRCA2 and Rad51 in response to DNA damage. Oncogene, 2008, 27(28), 3977-3985.
[http://dx.doi.org/10.1038/onc.2008.17] [PMID: 18317453]
[41]
Mendoza, J.; Sekiya, M.; Taniguchi, T.; Iijima, K.M.; Wang, R.; Ando, K. Global analysis of phosphorylation of tau by the checkpoint kinases Chk1 and Chk2 in vitro. J. Proteome Res., 2013, 12(6), 2654-2665.
[http://dx.doi.org/10.1021/pr400008f] [PMID: 23550703]
[42]
Iijima-Ando, K.; Zhao, L.; Gatt, A.; Shenton, C.; Iijima, K. A DNA damage-activated checkpoint kinase phosphorylates tau and enhances tau-induced neurodegeneration. Hum. Mol. Genet., 2010, 19(10), 1930-1938.
[http://dx.doi.org/10.1093/hmg/ddq068] [PMID: 20159774]
[43]
Li, G.; Yin, H.; Kuret, J. Casein kinase 1 delta phosphorylates tau and disrupts its binding to microtubules. J. Biol. Chem., 2004, 279(16), 15938-15945.
[http://dx.doi.org/10.1074/jbc.M314116200] [PMID: 14761950]
[44]
Hanger, D.P.; Byers, H.L.; Wray, S.; Leung, K.Y.; Saxton, M.J.; Seereeram, A.; Reynolds, C.H.; Ward, M.A.; Anderton, B.H. Novel phosphorylation sites in tau from Alzheimer brain support a role for casein kinase 1 in disease pathogenesis. J. Biol. Chem., 2007, 282(32), 23645-23654.
[http://dx.doi.org/10.1074/jbc.M703269200] [PMID: 17562708]
[45]
Lisman, J.; Schulman, H.; Cline, H. The molecular basis of CaMKII function in synaptic and behavioural memory. Nat. Rev. Neurosci., 2002, 3(3), 175-190.
[http://dx.doi.org/10.1038/nrn753] [PMID: 11994750]
[46]
Ghosh, A.; Giese, K.P. Calcium/calmodulin-dependent kinase II and Alzheimer’s disease. Mol. Brain, 2015, 8(1), 78.
[http://dx.doi.org/10.1186/s13041-015-0166-2] [PMID: 26603284]
[47]
Oka, M.; Fujisaki, N.; Maruko-Otake, A.; Ohtake, Y.; Shimizu, S.; Saito, T.; Hisanaga, S.I.; Iijima, K.M.; Ando, K. Ca2+/calmodulin-dependent protein kinase II promotes neurodegeneration caused by tau phosphorylated at Ser262/356 in a transgenic Drosophila model of tauopathy. J. Biochem., 2017, 162(5), 335-342.
[http://dx.doi.org/10.1093/jb/mvx038] [PMID: 28992057]
[48]
Beg, A.; Khan, F.I.; Lobb, K.A.; Islam, A.; Ahmad, F.; Hassan, M.I. High throughput screening, docking, and molecular dynamics studies to identify potential inhibitors of human calcium/calmodulin-dependent protein kinase IV. J. Biomol. Struct. Dyn., 2019, 37(8), 2179-2192.
[http://dx.doi.org/10.1080/07391102.2018.1479310] [PMID: 30044185]
[49]
Naz, H.; Jameel, E.; Hoda, N.; Shandilya, A.; Khan, P.; Islam, A.; Ahmad, F.; Jayaram, B.; Hassan, M.I. Structure guided design of potential inhibitors of human calcium-calmodulin dependent protein kinase IV containing pyrimidine scaffold. Bioorg. Med. Chem. Lett., 2016, 26(3), 782-788.
[http://dx.doi.org/10.1016/j.bmcl.2015.12.098] [PMID: 26783179]
[50]
Naz, H.; Khan, P.; Tarique, M.; Rahman, S.; Meena, A.; Ahamad, S.; Luqman, S.; Islam, A.; Ahmad, F.; Hassan, M.I. Binding studies and biological evaluation of β-carotene as a potential inhibitor of human calcium/calmodulin-dependent protein kinase IV. Int. J. Biol. Macromol., 2017, 96, 161-170.
[http://dx.doi.org/10.1016/j.ijbiomac.2016.12.024] [PMID: 27956097]
[51]
Umahara, T.; Uchihara, T.; Tsuchiya, K.; Nakamura, A.; Iwamoto, T.; Ikeda, K.; Takasaki, M. 14-3-3 proteins and zeta isoform containing neurofibrillary tangles in patients with Alzheimer’s disease. Acta Neuropathol., 2004, 108(4), 279-286.
[http://dx.doi.org/10.1007/s00401-004-0885-4] [PMID: 15235803]
[52]
Liu, S.J.; Zhang, J.Y.; Li, H.L.; Fang, Z.Y.; Wang, Q.; Deng, H.M.; Gong, C.X.; Grundke-Iqbal, I.; Iqbal, K.; Wang, J.Z. Tau becomes a more favorable substrate for GSK-3 when it is prephosphorylated by PKA in rat brain. J. Biol. Chem., 2004, 279(48), 50078-50088.
[http://dx.doi.org/10.1074/jbc.M406109200] [PMID: 15375165]
[53]
Liu, F.; Liang, Z.; Shi, J.; Yin, D.; El-Akkad, E.; Grundke-Iqbal, I.; Iqbal, K.; Gong, C.X. PKA modulates GSK-3beta- and cdk5-catalyzed phosphorylation of tau in site- and kinase-specific manners. FEBS Lett., 2006, 580(26), 6269-6274.
[http://dx.doi.org/10.1016/j.febslet.2006.10.033] [PMID: 17078951]
[54]
Carlyle, B.C.; Nairn, A.C.; Wang, M.; Yang, Y.; Jin, L.E.; Simen, A.A.; Ramos, B.P.; Bordner, K.A.; Craft, G.E.; Davies, P.; Pletikos, M.; Šestan, N.; Arnsten, A.F.; Paspalas, C.D. cAMP-PKA phosphorylation of tau confers risk for degeneration in aging association cortex. Proc. Natl. Acad. Sci. USA, 2014, 111(13), 5036-5041.
[http://dx.doi.org/10.1073/pnas.1322360111] [PMID: 24707050]
[55]
Lee, G. Tau and src family tyrosine kinases. Biochim. Biophys. Acta, 2005, 1739(2-3), 323-330.
[http://dx.doi.org/10.1016/j.bbadis.2004.09.002] [PMID: 15615649]
[56]
Scales, T.M.; Derkinderen, P.; Leung, K.Y.; Byers, H.L.; Ward, M.A.; Price, C.; Bird, I.N.; Perera, T.; Kellie, S.; Williamson, R.; Anderton, B.H.; Reynolds, C.H. Tyrosine phosphorylation of tau by the SRC family kinases lck and fyn. Mol. Neurodegener., 2011, 6, 12.
[http://dx.doi.org/10.1186/1750-1326-6-12] [PMID: 21269457]
[57]
Reynolds, C.H.; Garwood, C.J.; Wray, S.; Price, C.; Kellie, S.; Perera, T.; Zvelebil, M.; Yang, A.; Sheppard, P.W.; Varndell, I.M.; Hanger, D.P.; Anderton, B.H. Phosphorylation regulates tau interactions with Src homology 3 domains of phosphatidylinositol 3-kinase, phospholipase Cgamma1, Grb2, and Src family kinases. J. Biol. Chem., 2008, 283(26), 18177-18186.
[http://dx.doi.org/10.1074/jbc.M709715200] [PMID: 18467332]
[58]
Nygaard, H.B. Targeting fyn kinase in alzheimer’s disease. Biol. Psychiatry, 2018, 83(4), 369-376.
[http://dx.doi.org/10.1016/j.biopsych.2017.06.004] [PMID: 28709498]
[59]
Nygaard, H.B.; van Dyck, C.H.; Strittmatter, S.M. Fyn kinase inhibition as a novel therapy for Alzheimer’s disease. Alzheimers Res. Ther., 2014, 6(1), 8.
[http://dx.doi.org/10.1186/alzrt238] [PMID: 24495408]
[60]
Lau, D.H.; Hogseth, M.; Phillips, E.C.; O’Neill, M.J.; Pooler, A.M.; Noble, W.; Hanger, D.P. Critical residues involved in tau binding to fyn: implications for tau phosphorylation in Alzheimer’s disease. Acta Neuropathol. Commun., 2016, 4(1), 49.
[http://dx.doi.org/10.1186/s40478-016-0317-4] [PMID: 27193083]
[61]
Zahratka, J.A.; Shao, Y.; Shaw, M.; Todd, K.; Formica, S.V.; Khrestian, M.; Montine, T.; Leverenz, J.B.; Bekris, L.M. Regulatory region genetic variation is associated with FYN expression in Alzheimer’s disease. Neurobiol. Aging, 2017, 51, 43-53.
[http://dx.doi.org/10.1016/j.neurobiolaging.2016.11.001] [PMID: 28033507]
[62]
Derkinderen, P.; Scales, T.M.; Hanger, D.P.; Leung, K.Y.; Byers, H.L.; Ward, M.A.; Lenz, C.; Price, C.; Bird, I.N.; Perera, T.; Kellie, S.; Williamson, R.; Noble, W.; Van Etten, R.A.; Leroy, K.; Brion, J.P.; Reynolds, C.H.; Anderton, B.H. Tyrosine 394 is phosphorylated in Alzheimer’s paired helical filament tau and in fetal tau with c-Abl as the candidate tyrosine kinase. J. Neurosci., 2005, 25(28), 6584-6593.
[http://dx.doi.org/10.1523/JNEUROSCI.1487-05.2005] [PMID: 16014719]
[63]
Tremblay, M.A.; Acker, C.M.; Davies, P. Tau phosphorylated at tyrosine 394 is found in Alzheimer’s disease tangles and can be a product of the Abl-related kinase, Arg. J. Alzheimers Dis., 2010, 19(2), 721-733.
[http://dx.doi.org/10.3233/JAD-2010-1271] [PMID: 20110615]
[64]
Viola, K.L.; Klein, W.L. Amyloid β oligomers in Alzheimer’s disease pathogenesis, treatment, and diagnosis. Acta Neuropathol., 2015, 129(2), 183-206.
[http://dx.doi.org/10.1007/s00401-015-1386-3] [PMID: 25604547]
[65]
Gong, C.X.; Grundke-Iqbal, I.; Iqbal, K. Targeting tau protein in Alzheimer’s disease. Drugs Aging, 2010, 27(5), 351-365.
[http://dx.doi.org/10.2165/11536110-000000000-00000] [PMID: 20450234]
[66]
Hong-Qi, Y.; Zhi-Kun, S.; Sheng-Di, C. Current advances in the treatment of Alzheimer’s disease: focused on considerations targeting Aβ and tau. Transl. Neurodegener., 2012, 1(1), 21.
[http://dx.doi.org/10.1186/2047-9158-1-21] [PMID: 23210837]
[67]
Ibrahim, M.M.; Gabr, M.T. Multitarget therapeutic strategies for Alzheimer’s disease. Neural Regen. Res., 2019, 14(3), 437-440.
[http://dx.doi.org/10.4103/1673-5374.245463] [PMID: 30539809]
[68]
Godyń, J.; Jończyk, J.; Panek, D.; Malawska, B. Therapeutic strategies for Alzheimer’s disease in clinical trials. Pharmacol. Rep., 2016, 68(1), 127-138.
[http://dx.doi.org/10.1016/j.pharep.2015.07.006] [PMID: 26721364]
[69]
Hung, S.Y.; Fu, W.M. Drug candidates in clinical trials for Alzheimer’s disease. J. Biomed. Sci., 2017, 24(1), 47.
[http://dx.doi.org/10.1186/s12929-017-0355-7] [PMID: 28720101]
[70]
Cao, J.; Hou, J.; Ping, J.; Cai, D. Advances in developing novel therapeutic strategies for Alzheimer’s disease. Mol. Neurodegener., 2018, 13(1), 64.
[http://dx.doi.org/10.1186/s13024-018-0299-8] [PMID: 30541602]
[71]
Aneja, B.; Khan, N.S.; Khan, P.; Queen, A.; Hussain, A.; Rehman, M.T.; Alajmi, M.F.; El-Seedi, H.R.; Ali, S.; Hassan, M.I.; Abid, M. Design and development of Isatin-triazole hydrazones as potential inhibitors of microtubule affinity-regulating kinase 4 for the therapeutic management of cell proliferation and metastasis. Eur. J. Med. Chem., 2019, 163, 840-852.
[http://dx.doi.org/10.1016/j.ejmech.2018.12.026] [PMID: 30579124]
[72]
Naqvi, A.A.T.; Mohammad, T.; Hasan, G.M.; Hassan, M.I. Advancements in docking and molecular dynamics simulations towards ligand-receptor interactions and structure-function relationships. Curr. Top. Med. Chem., 2018, 18(20), 1755-1768.
[http://dx.doi.org/10.2174/1568026618666181025114157] [PMID: 30360721]
[73]
Parveen, I.; Khan, P.; Ali, S.; Hassan, M.I.; Ahmed, N. Synthesis, molecular docking and inhibition studies of novel 3-N-aryl substituted-2-heteroarylchromones targeting microtubule affinity regulating kinase 4 inhibitors. Eur. J. Med. Chem., 2018, 159, 166-177.
[http://dx.doi.org/10.1016/j.ejmech.2018.09.030] [PMID: 30290280]
[74]
Naz, H.; Tarique, M.; Khan, P.; Luqman, S.; Ahamad, S.; Islam, A.; Ahmad, F.; Hassan, M.I. Evidence of vanillin binding to CAMKIV explains the anti-cancer mechanism in human hepatic carcinoma and neuroblastoma cells. Mol. Cell. Biochem., 2018, 438(1-2), 35-45.
[http://dx.doi.org/10.1007/s11010-017-3111-0] [PMID: 28744811]
[75]
Hulcová, D.; Maříková, J.; Korábečný, J.; Hošťálková, A.; Jun, D.; Kuneš, J.; Chlebek, J.; Opletal, L.; De Simone, A.; Nováková, L.; Andrisano, V.; Růžička, A.; Cahlíková, L. Amaryllidaceae alkaloids from Narcissus pseudonarcissus L. cv. Dutch Master as potential drugs in treatment of Alzheimer’s disease. Phytochemistry, 2019, 165 112055
[http://dx.doi.org/10.1016/j.phytochem.2019.112055] [PMID: 31261031]
[76]
Heider, F.; Ansideri, F.; Tesch, R.; Pantsar, T.; Haun, U.; Döring, E.; Kudolo, M.; Poso, A.; Albrecht, W.; Laufer, S.A.; Koch, P. Pyridinylimidazoles as dual glycogen synthase kinase 3β/p38α mitogen-activated protein kinase inhibitors. Eur. J. Med. Chem., 2019, 175, 309-329.
[http://dx.doi.org/10.1016/j.ejmech.2019.04.035] [PMID: 31096153]
[77]
Shi, X.L.; Wu, J.D.; Liu, P.; Liu, Z.P. Synthesis and evaluation of novel GSK-3β inhibitors as multifunctional agents against Alzheimer’s disease. Eur. J. Med. Chem., 2019, 167, 211-225.
[http://dx.doi.org/10.1016/j.ejmech.2019.02.001] [PMID: 30772605]
[78]
Bisi, A.; Arribas, R.L.; Micucci, M.; Budriesi, R.; Feoli, A.; Castellano, S.; Belluti, F.; Gobbi, S.; de Los Rios, C.; Rampa, A. Polycyclic maleimide-based derivatives as first dual modulators of neuronal calcium channels and GSK-3β for Alzheimer’s disease treatment. Eur. J. Med. Chem., 2019, 163, 394-402.
[http://dx.doi.org/10.1016/j.ejmech.2018.12.003] [PMID: 30530190]
[79]
Liang, Z.; Li, Q.X. Discovery of selective, substrate-competitive, and passive membrane permeable glycogen synthase kinase-3beta inhibitors: Synthesis, biological evaluation, and molecular modeling of new c-glycosylflavones. ACS Chem. Neurosci., 2018, 9(5), 1166-1183.
[http://dx.doi.org/10.1021/acschemneuro.8b00010] [PMID: 29381861]
[80]
Gameiro, I.; Michalska, P.; Tenti, G.; Cores, Á.; Buendia, I.; Rojo, A.I.; Georgakopoulos, N.D.; Hernández-Guijo, J.M.; Teresa Ramos, M.; Wells, G.; López, M.G.; Cuadrado, A.; Menéndez, J.C.; León, R. Discovery of the first dual GSK3β inhibitor/Nrf2 inducer. A new multitarget therapeutic strategy for Alzheimer’s disease. Sci. Rep., 2017, 7, 45701.
[http://dx.doi.org/10.1038/srep45701] [PMID: 28361919]
[81]
Calkins, M.J.; Johnson, D.A.; Townsend, J.A.; Vargas, M.R.; Dowell, J.A.; Williamson, T.P.; Kraft, A.D.; Lee, J.M.; Li, J.; Johnson, J.A. The Nrf2/ARE pathway as a potential therapeutic target in neurodegenerative disease. Antioxid. Redox Signal., 2009, 11(3), 497-508.
[http://dx.doi.org/10.1089/ars.2008.2242] [PMID: 18717629]
[82]
Matsunaga, S.; Fujishiro, H.; Takechi, H. Efficacy and safety of glycogen synthase kinase 3 inhibitors for alzheimer’s disease: A systematic review and meta-analysis. J. Alzheimers Dis., 2019, 69(4), 1031-1039.
[http://dx.doi.org/10.3233/JAD-190256] [PMID: 31156177]
[83]
Palomo, V.; Martinez, A. Glycogen synthase kinase 3 (GSK-3) inhibitors: a patent update (2014-2015). Expert Opin. Ther. Pat., 2017, 27(6), 657-666.
[http://dx.doi.org/10.1080/13543776.2017.1259412] [PMID: 27828716]
[84]
Mushtaq, G.; Greig, N.H.; Anwar, F.; Al-Abbasi, F.A.; Zamzami, M.A.; Al-Talhi, H.A.; Kamal, M.A. Neuroprotective mechanisms mediated by cdk5 inhibition. Curr. Pharm. Des., 2016, 22(5), 527-534.
[http://dx.doi.org/10.2174/1381612822666151124235028] [PMID: 26601962]
[85]
Seo, J.; Kritskiy, O.; Watson, L.A.; Barker, S.J.; Dey, D.; Raja, W.K.; Lin, Y.T.; Ko, T.; Cho, S.; Penney, J.; Silva, M.C.; Sheridan, S.D.; Lucente, D.; Gusella, J.F.; Dickerson, B.C.; Haggarty, S.J.; Tsai, L.H. Inhibition of p25/cdk5 attenuates tauopathy in mouse and ipsc models of frontotemporal dementia. J. Neurosci., 2017, 37(41), 9917-9924.
[http://dx.doi.org/10.1523/JNEUROSCI.0621-17.2017] [PMID: 28912154]
[86]
Liu, Y.; Cao, L.; Zhang, X.; Liang, Y.; Xu, Y.; Zhu, C. Memantine differentially regulates tau phosphorylation induced by chronic restraint stress of varying duration in mice. Neural Plast., 2019, 2019 4168472
[http://dx.doi.org/10.1155/2019/4168472] [PMID: 30906318]
[87]
Hédou, D.; Godeau, J.; Loaëc, N.; Meijer, L.; Fruit, C.; Besson, T. Synthesis of thiazolo[5,4-f]quinazolin-9(8h)-ones as multi-target directed ligands of ser/thr kinases. Molecules, 2016, 21(5) E578
[http://dx.doi.org/10.3390/molecules21050578] [PMID: 27144552]
[88]
Zeinyeh, W.; Esvan, Y.J.; Nauton, L.; Loaëc, N.; Meijer, L.; Théry, V.; Anizon, F.; Giraud, F.; Moreau, P. Synthesis and preliminary in vitro kinase inhibition evaluation of new diversely substituted pyrido[3,4-g]quinazoline derivatives. Bioorg. Med. Chem. Lett., 2016, 26(17), 4327-4329.
[http://dx.doi.org/10.1016/j.bmcl.2016.07.032] [PMID: 27469128]
[89]
Kidger, A.M.; Sipthorp, J.; Cook, S.J. ERK1/2 inhibitors: New weapons to inhibit the RAS-regulated RAF-MEK1/2-ERK1/2 pathway. Pharmacol. Ther., 2018, 187, 45-60.
[http://dx.doi.org/10.1016/j.pharmthera.2018.02.007] [PMID: 29454854]
[90]
Morroni, F.; Sita, G.; Graziosi, A.; Ravegnini, G.; Molteni, R.; Paladini, M.S.; Dias, K.S.T.; Dos Santos, A.F.; Viegas, C., Jr; Camps, I.; Pruccoli, L.; Tarozzi, A.; Hrelia, P. Pqm130, a novel feruloyl-donepezil hybrid compound, effectively ameliorates the cognitive impairments and pathology in a mouse model of alzheimer’s disease. Front. Pharmacol., 2019, 10, 658.
[http://dx.doi.org/10.3389/fphar.2019.00658] [PMID: 31244664]
[91]
Siano, G.; Caiazza, M.C.; Ollà, I.; Varisco, M.; Madaro, G.; Quercioli, V.; Calvello, M.; Cattaneo, A.; Di Primio, C. Identification of an erk inhibitor as a therapeutic drug against tau aggregation in a new cell-based assay. Front. Cell. Neurosci., 2019, 13, 386.
[http://dx.doi.org/10.3389/fncel.2019.00386] [PMID: 31496937]
[92]
Kheiri, G.; Dolatshahi, M.; Rahmani, F.; Rezaei, N. Role of p38/MAPKs in Alzheimer’s disease: implications for amyloid beta toxicity targeted therapy. Rev. Neurosci., 2018, 30(1), 9-30.
[http://dx.doi.org/10.1515/revneuro-2018-0008] [PMID: 29804103]
[93]
Lee, J.K.; Kim, N.J. Recent advances in the inhibition of p38 mapk as a potential strategy for the treatment of alzheimer’s disease. Molecules, 2017, 22(8) E1287
[http://dx.doi.org/10.3390/molecules22081287] [PMID: 28767069]
[94]
Casadomé-Perales, Á.; Matteis, L.; Alleva, M.; Infantes-Rodríguez, C.; Palomares-Pérez, I.; Saito, T.; Saido, T.C.; Esteban, J.A.; Nebreda, A.R.; de la Fuente, J.M.; Dotti, C.G. Inhibition of p38 MAPK in the brain through nasal administration of p38 inhibitor loaded in chitosan nanocapsules. Nanomedicine (Lond.), 2019, 14(18), 2409-2422.
[http://dx.doi.org/10.2217/nnm-2018-0496] [PMID: 31456488]
[95]
Yarza, R.; Vela, S.; Solas, M.; Ramirez, M.J. C-jun n-terminal kinase (jnk) signaling as a therapeutic target for alzheimer’s disease. Front. Pharmacol., 2016, 6, 321.
[http://dx.doi.org/10.3389/fphar.2015.00321] [PMID: 26793112]
[96]
Bennett, B.L.; Sasaki, D.T.; Murray, B.W.; O’Leary, E.C.; Sakata, S.T.; Xu, W.; Leisten, J.C.; Motiwala, A.; Pierce, S.; Satoh, Y.; Bhagwat, S.S.; Manning, A.M.; Anderson, D.W. SP600125, an anthrapyrazolone inhibitor of Jun N-terminal kinase. Proc. Natl. Acad. Sci. USA, 2001, 98(24), 13681-13686.
[http://dx.doi.org/10.1073/pnas.251194298] [PMID: 11717429]
[97]
Maroney, A.C.; Finn, J.P.; Connors, T.J.; Durkin, J.T.; Angeles, T.; Gessner, G.; Xu, Z.; Meyer, S.L.; Savage, M.J.; Greene, L.A.; Scott, R.W.; Vaught, J.L. Cep-1347 (KT7515), a semisynthetic inhibitor of the mixed lineage kinase family. J. Biol. Chem., 2001, 276(27), 25302-25308.
[http://dx.doi.org/10.1074/jbc.M011601200] [PMID: 11325962]
[98]
Angell, R.M.; Atkinson, F.L.; Brown, M.J.; Chuang, T.T.; Christopher, J.A.; Cichy-Knight, M.; Dunn, A.K.; Hightower, K.E.; Malkakorpi, S.; Musgrave, J.R.; Neu, M.; Rowland, P.; Shea, R.L.; Smith, J.L.; Somers, D.O.; Thomas, S.A.; Thompson, G.; Wang, R. N-(3-Cyano-4,5,6,7-tetrahydro-1-benzothien-2-yl)amides as potent, selective, inhibitors of JNK2 and JNK3. Bioorg. Med. Chem. Lett., 2007, 17(5), 1296-1301.
[http://dx.doi.org/10.1016/j.bmcl.2006.12.003] [PMID: 17194588]
[99]
Gaillard, P.; Jeanclaude-Etter, I.; Ardissone, V.; Arkinstall, S.; Cambet, Y.; Camps, M.; Chabert, C.; Church, D.; Cirillo, R.; Gretener, D.; Halazy, S.; Nichols, A.; Szyndralewiez, C.; Vitte, P.A.; Gotteland, J.P. Design and synthesis of the first generation of novel potent, selective, and in vivo active (benzothiazol-2-yl)acetonitrile inhibitors of the c-Jun N-terminal kinase. J. Med. Chem., 2005, 48(14), 4596-4607.
[http://dx.doi.org/10.1021/jm0310986] [PMID: 15999997]
[100]
Zhang, T.; Inesta-Vaquera, F.; Niepel, M.; Zhang, J.; Ficarro, S.B.; Machleidt, T.; Xie, T.; Marto, J.A.; Kim, N.; Sim, T.; Laughlin, J.D.; Park, H.; LoGrasso, P.V.; Patricelli, M.; Nomanbhoy, T.K.; Sorger, P.K.; Alessi, D.R.; Gray, N.S. Discovery of potent and selective covalent inhibitors of JNK. Chem. Biol., 2012, 19(1), 140-154.
[http://dx.doi.org/10.1016/j.chembiol.2011.11.010] [PMID: 22284361]
[101]
Chin, J.Y.; Knowles, R.B.; Schneider, A.; Drewes, G.; Mandelkow, E.M.; Hyman, B.T. Microtubule-affinity regulating kinase (MARK) is tightly associated with neurofibrillary tangles in Alzheimer brain: a fluorescence resonance energy transfer study. J. Neuropathol. Exp. Neurol., 2000, 59(11), 966-971.
[http://dx.doi.org/10.1093/jnen/59.11.966] [PMID: 11089574]
[102]
Timm, T.; von Kries, J.P.; Li, X.; Zempel, H.; Mandelkow, E.; Mandelkow, E.M. Microtubule affinity regulating kinase activity in living neurons was examined by a genetically encoded fluorescence resonance energy transfer/fluorescence lifetime imaging-based biosensor: inhibitors with therapeutic potential. J. Biol. Chem., 2011, 286(48), 41711-41722.
[http://dx.doi.org/10.1074/jbc.M111.257865] [PMID: 21984823]
[103]
Khan, P.; Rahman, S.; Queen, A.; Manzoor, S.; Naz, F.; Hasan, G.M.; Luqman, S.; Kim, J.; Islam, A.; Ahmad, F.; Hassan, M.I. Elucidation of dietary polyphenolics as potential inhibitor of microtubule affinity regulating kinase 4: In silico and in vitro studies. Sci. Rep., 2017, 7(1), 9470.
[http://dx.doi.org/10.1038/s41598-017-09941-4] [PMID: 28842631]
[104]
Naz, F.; Khan, F.I.; Mohammad, T.; Khan, P.; Manzoor, S.; Hasan, G.M.; Lobb, K.A.; Luqman, S.; Islam, A.; Ahmad, F.; Hassan, M.I. Investigation of molecular mechanism of recognition between citral and mark4: A newer therapeutic approach to attenuate cancer cell progression. Int J Biol Macromol, 2018, 107(Pt B), 2580-2589.
[http://dx.doi.org/10.1016/j.ijbiomac.2017.10.143]
[105]
Voura, M.; Khan, P.; Thysiadis, S.; Katsamakas, S.; Queen, A.; Hasan, G.M.; Ali, S.; Sarli, V.; Hassan, M.I. Probing the inhibition of microtubule affinity regulating kinase 4 by n-substituted acridones. Sci. Rep., 2019, 9(1), 1676.
[http://dx.doi.org/10.1038/s41598-018-38217-8] [PMID: 30737440]
[106]
Naqvi, A.A.T.; Jairajpuri, D.S.; Noman, O.M.A.; Hussain, A.; Islam, A.; Ahmad, F.; Alajmi, M.F.; Hassan, M.I. Evaluation of pyrazolopyrimidine derivatives as microtubule affinity regulating kinase 4 inhibitors: Towards therapeutic management of Alzheimer’s disease. J. Biomol. Struct. Dyn., 2019, 1-16.
[http://dx.doi.org/10.1080/07391102.2019.1666745] [PMID: 31512980]
[107]
Shen, X.; Liu, X.; Wan, S.; Fan, X.; He, H.; Wei, R.; Pu, W.; Peng, Y.; Wang, C. Discovery of coumarin as microtubule affinity-regulating kinase 4 inhibitor that sensitize hepatocellular carcinoma to paclitaxel. Front Chem., 2019, 7, 366.
[http://dx.doi.org/10.3389/fchem.2019.00366] [PMID: 31179271]
[108]
Xue, Y.; Wan, P.T.; Hillertz, P.; Schweikart, F.; Zhao, Y.; Wissler, L.; Dekker, N. X-ray structural analysis of tau-tubulin kinase 1 and its interactions with small molecular inhibitors. ChemMedChem, 2013, 8(11), 1846-1854.
[http://dx.doi.org/10.1002/cmdc.201300274] [PMID: 24039150]
[109]
Kiefer, S.E.; Chang, C.J.; Kimura, S.R.; Gao, M.; Xie, D.; Zhang, Y.; Zhang, G.; Gill, M.B.; Mastalerz, H.; Thompson, L.A.; Cacace, A.M.; Sheriff, S. The structure of human tau-tubulin kinase 1 both in the apo form and in complex with an inhibitor. Acta Crystallogr. F Struct. Biol. Commun., 2014, 70(Pt 2), 173-181.
[http://dx.doi.org/10.1107/S2053230X14000144] [PMID: 24637750]
[110]
Zabludoff, S.D.; Deng, C.; Grondine, M.R.; Sheehy, A.M.; Ashwell, S.; Caleb, B.L.; Green, S.; Haye, H.R.; Horn, C.L.; Janetka, J.W.; Liu, D.; Mouchet, E.; Ready, S.; Rosenthal, J.L.; Queva, C.; Schwartz, G.K.; Taylor, K.J.; Tse, A.N.; Walker, G.E.; White, A.M. AZD7762, a novel checkpoint kinase inhibitor, drives checkpoint abrogation and potentiates DNA-targeted therapies. Mol. Cancer Ther., 2008, 7(9), 2955-2966.
[http://dx.doi.org/10.1158/1535-7163.MCT-08-0492] [PMID: 18790776]
[111]
Guzi, T.J.; Paruch, K.; Dwyer, M.P.; Labroli, M.; Shanahan, F.; Davis, N.; Taricani, L.; Wiswell, D.; Seghezzi, W.; Penaflor, E.; Bhagwat, B.; Wang, W.; Gu, D.; Hsieh, Y.; Lee, S.; Liu, M.; Parry, D. Targeting the replication checkpoint using SCH 900776, a potent and functionally selective CHK1 inhibitor identified via high content screening. Mol. Cancer Ther., 2011, 10(4), 591-602.
[http://dx.doi.org/10.1158/1535-7163.MCT-10-0928] [PMID: 21321066]
[112]
Adler, P.; Mayne, J.; Walker, K.; Ning, Z.; Figeys, D. Therapeutic targeting of casein kinase 1delta/epsilon in an alzheimer’s disease mouse model. J. Proteome Res., 2019, 18(9), 3383-3393.
[http://dx.doi.org/10.1021/acs.jproteome.9b00312] [PMID: 31334659]
[113]
Moriguchi, S.; Kita, S.; Fukaya, M.; Osanai, M.; Inagaki, R.; Sasaki, Y.; Izumi, H.; Horie, K.; Takeda, J.; Saito, T.; Sakagami, H.; Saido, T.C.; Iwamoto, T.; Fukunaga, K. Reduced expression of Na+/Ca2+ exchangers is associated with cognitive deficits seen in Alzheimer’s disease model mice. Neuropharmacology, 2018, 131, 291-303.
[http://dx.doi.org/10.1016/j.neuropharm.2017.12.037] [PMID: 29274751]
[114]
Pellicena, P.; Schulman, H. CaMKII inhibitors: from research tools to therapeutic agents. Front. Pharmacol., 2014, 5, 21.
[http://dx.doi.org/10.3389/fphar.2014.00021] [PMID: 24600394]
[115]
Li, H.; Yang, S.; Wu, J.; Ji, L.; Zhu, L.; Cao, L.; Huang, J.; Jiang, Q.; Wei, J.; Liu, M.; Mao, K.; Wei, N.; Xie, W.; Yang, Z. cAMP/PKA signaling pathway contributes to neuronal apoptosis via regulating IDE expression in a mixed model of type 2 diabetes and Alzheimer’s disease. J. Cell. Biochem., 2018, 119(2), 1616-1626.
[http://dx.doi.org/10.1002/jcb.26321] [PMID: 28771808]
[116]
Murray, A.J. Pharmacological PKA inhibition: all may not be what it seems. Sci. Signal., 2008, 1(22), re4.
[http://dx.doi.org/10.1126/scisignal.122re4] [PMID: 18523239]
[117]
Amini, E.; Nassireslami, E.; Payandemehr, B.; Khodagholi, F.; Foolad, F.; Khalaj, S.; Hamedani, M.P.; Azimi, L.; Sharifzadeh, M. Paradoxical role of PKA inhibitor on amyloidβ-induced memory deficit. Physiol. Behav., 2015, 149, 76-85.
[http://dx.doi.org/10.1016/j.physbeh.2015.05.029] [PMID: 26037462]
[118]
Gubens, M.A.; Burns, M.; Perkins, S.M.; Pedro-Salcedo, M.S.; Althouse, S.K.; Loehrer, P.J.; Wakelee, H.A. A phase II study of saracatinib (AZD0530), a Src inhibitor, administered orally daily to patients with advanced thymic malignancies. Lung Cancer, 2015, 89(1), 57-60.
[http://dx.doi.org/10.1016/j.lungcan.2015.04.008] [PMID: 26009269]
[119]
Liu, W.; Zhao, J.; Lu, G. miR-106b inhibits tau phosphorylation at Tyr18 by targeting Fyn in a model of Alzheimer’s disease. Biochem. Biophys. Res. Commun., 2016, 478(2), 852-857.
[http://dx.doi.org/10.1016/j.bbrc.2016.08.037] [PMID: 27520374]
[120]
Santos, F.P.; Kantarjian, H.; Cortes, J.; Quintas-Cardama, A. Bafetinib, a dual Bcr-Abl/Lyn tyrosine kinase inhibitor for the potential treatment of leukemia. Curr. Opin. Investig. Drugs, 2010, 11(12), 1450-1465.
[PMID: 21154127]
[121]
Lee, S.; Kim, S.; Park, Y.J.; Yun, S.P.; Kwon, S.H.; Kim, D.; Kim, D.Y.; Shin, J.S.; Cho, D.J.; Lee, G.Y.; Ju, H.S.; Yun, H.J.; Park, J.H.; Kim, W.R.; Jung, E.A.; Lee, S.; Ko, H.S. The c-Abl inhibitor, Radotinib HCl, is neuroprotective in a preclinical Parkinson’s disease mouse model. Hum. Mol. Genet., 2018, 27(13), 2344-2356.
[http://dx.doi.org/10.1093/hmg/ddy143] [PMID: 29897434]
[122]
Fowler, A.J.; Hebron, M.; Missner, A.A.; Wang, R.; Gao, X.; Kurd-Misto, B.T.; Liu, X.; Moussa, C.E. Multikinase abl/ddr/src inhibition produces optimal effects for tyrosine kinase inhibition in neurodegeneration. Drugs R D., 2019, 19(2), 149-166.
[http://dx.doi.org/10.1007/s40268-019-0266-z] [PMID: 30919310]
[123]
Cummings, J.; Lee, G.; Ritter, A.; Sabbagh, M.; Zhong, K. Alzheimer’s disease drug development pipeline: 2019. Alzheimers Dement. (N. Y.), 2019, 5, 272-293.
[http://dx.doi.org/10.1016/j.trci.2019.05.008] [PMID: 31334330]
[124]
Medina, M. An overview on the clinical development of tau-based therapeutics. Int. J. Mol. Sci., 2018, 19(4) E1160
[http://dx.doi.org/10.3390/ijms19041160] [PMID: 29641484]
[125]
van Dyck, C.H.; Nygaard, H.B.; Chen, K.; Donohue, M.C.; Raman, R.; Rissman, R.A.; Brewer, J.B.; Koeppe, R.A.; Chow, T.W.; Rafii, M.S.; Gessert, D.; Choi, J.; Turner, R.S.; Kaye, J.A.; Gale, S.A.; Reiman, E.M.; Aisen, P.S.; Strittmatter, S.M. Effect of azd0530 on cerebral metabolic decline in alzheimer disease: A randomized clinical trial. JAMA Neurol., 2019. Epub ahead of print
[http://dx.doi.org/10.1001/jamaneurol.2019.2050] [PMID: 31329216]

Rights & Permissions Print Export Cite as
© 2024 Bentham Science Publishers | Privacy Policy