Recent Advances in Drug Repurposing for Parkinson’s Disease

Author(s): Xin Chen*, Giuseppe Gumina, Kristopher G. Virga.

Journal Name: Current Medicinal Chemistry

Volume 26 , Issue 28 , 2019

  Journal Home
Translate in Chinese
Become EABM
Become Reviewer

Abstract:

As a long-term degenerative disorder of the central nervous system that mostly affects older people, Parkinson’s disease is a growing health threat to our ever-aging population. Despite remarkable advances in our understanding of this disease, all therapeutics currently available only act to improve symptoms but cannot stop the disease progression. Therefore, it is essential that more effective drug discovery methods and approaches are developed, validated, and used for the discovery of disease-modifying treatments for Parkinson’s disease. Drug repurposing, also known as drug repositioning, or the process of finding new uses for existing or abandoned pharmaceuticals, has been recognized as a cost-effective and timeefficient way to develop new drugs, being equally promising as de novo drug discovery in the field of neurodegeneration and, more specifically for Parkinson’s disease. The availability of several established libraries of clinical drugs and fast evolvement in disease biology, genomics and bioinformatics has stimulated the momentums of both in silico and activity-based drug repurposing. With the successful clinical introduction of several repurposed drugs for Parkinson’s disease, drug repurposing has now become a robust alternative approach to the discovery and development of novel drugs for this disease. In this review, recent advances in drug repurposing for Parkinson’s disease will be discussed.

Keywords: Drug repurposing, Parkinson’s disease, neurodegeneration, dopamine, α-synuclein, neuroinflammation, neuroprotection.

[1]
Gibrat, C.; Saint-Pierre, M.; Bousquet, M.; Lévesque, D.; Rouillard, C.; Cicchetti, F. Differences between subacute and chronic MPTP mice models: investigation of dopaminergic neuronal degeneration and alpha-synuclein inclusions. J. Neurochem., 2009, 109(5), 1469-1482.
[http://dx.doi.org/10.1111/j.1471-4159.2009.06072.x] [PMID: 19457163]
[2]
Rodriguez-Oroz, M.C.; Jahanshahi, M.; Krack, P.; Litvan, I.; Macias, R.; Bezard, E.; Obeso, J.A. Initial clinical manifestations of Parkinson’s disease: features and pathophysiological mechanisms. Lancet Neurol., 2009, 8(12), 1128-1139.
[http://dx.doi.org/10.1016/S1474-4422(09)70293-5] [PMID: 19909911]
[3]
Rana, A.Q.; Ahmed, U.S.; Chaudry, Z.M.; Vasan, S. Parkinson’s disease: A review of non-motor symptoms. Expert Rev. Neurother., 2015, 15(5), 549-562.
[http://dx.doi.org/10.1586/14737175.2015.1038244] [PMID: 25936847]
[4]
Shulman, J.M.; De Jager, P.L.; Feany, M.B. Parkinson’s disease: Genetics and pathogenesis. Annu. Rev. Pathol., 2011, 6, 193-222.
[http://dx.doi.org/10.1146/annurev-pathol-011110-130242] [PMID: 21034221]
[5]
Dorsey, E.R.; Constantinescu, R.; Thompson, J.P.; Biglan, K.M.; Holloway, R.G.; Kieburtz, K.; Marshall, F.J.; Ravina, B.M.; Schifitto, G.; Siderowf, A.; Tanner, C.M. Projected number of people with Parkinson disease in the most populous nations, 2005 through 2030. Neurology, 2007, 68(5), 384-386.
[http://dx.doi.org/10.1212/01.wnl.0000247740.47667.03] [PMID: 17082464]
[6]
Samii, A.; Nutt, J.G.; Ransom, B.R. Parkinson’s disease. Lancet, 2004, 363(9423), 1783-1793.
[http://dx.doi.org/10.1016/S0140-6736(04)16305-8] [PMID: 15172778]
[7]
Dickson, D.W. Parkinson’s disease and parkinsonism: neuropathology. Cold Spring Harb. Perspect. Med., 2012, 2(8)a009258
[http://dx.doi.org/10.1101/cshperspect.a009258] [PMID: 22908195]
[8]
Antony, P.M.; Diederich, N.J.; Krüger, R.; Balling, R. The hallmarks of Parkinson’s disease. FEBS J., 2013, 280(23), 5981-5993.
[http://dx.doi.org/10.1111/febs.12335] [PMID: 23663200]
[9]
Przedborski, S. The two-century journey of Parkinson disease research. Nat. Rev. Neurosci., 2017, 18(4), 251-259.
[http://dx.doi.org/10.1038/nrn.2017.25] [PMID: 28303016]
[10]
Simón-Sánchez, J.; Schulte, C.; Bras, J.M.; Sharma, M.; Gibbs, J.R.; Berg, D.; Paisan-Ruiz, C.; Lichtner, P.; Scholz, S.W.; Hernandez, D.G.; Krüger, R.; Federoff, M.; Klein, C.; Goate, A.; Perlmutter, J.; Bonin, M.; Nalls, M.A.; Illig, T.; Gieger, C.; Houlden, H.; Steffens, M.; Okun, M.S.; Racette, B.A.; Cookson, M.R.; Foote, K.D.; Fernandez, H.H.; Traynor, B.J.; Schreiber, S.; Arepalli, S.; Zonozi, R.; Gwinn, K.; van der Brug, M.; Lopez, G.; Chanock, S.J.; Schatzkin, A.; Park, Y.; Hollenbeck, A.; Gao, J.; Huang, X.; Wood, N.W.; Lorenz, D.; Deuschl, G.; Chen, H.; Riess, O.; Hardy, J.A.; Singleton, A.B.; Gasser, T. Genome-wide association study reveals genetic risk underlying Parkinson’s disease. Nat. Genet., 2009, 41(12), 1308-1312.
[http://dx.doi.org/10.1038/ng.487] [PMID: 19915575]
[11]
Schneider, S.A.; Alcalay, R.N. Neuropathology of genetic synucleinopathies with parkinsonism: Review of the literature. Mov. Disord., 2017, 32(11), 1504-1523.
[http://dx.doi.org/10.1002/mds.27193] [PMID: 29124790]
[12]
Kalia, L.V.; Lang, A.E. Parkinson’s disease. Lancet, 2015, 386(9996), 896-912.
[http://dx.doi.org/10.1016/S0140-6736(14)61393-3] [PMID: 25904081]
[13]
Swinney, D.C.; Anthony, J. How were new medicines discovered? Nat. Rev. Drug Discov., 2011, 10(7), 507-519.
[http://dx.doi.org/10.1038/nrd3480] [PMID: 21701501]
[14]
Mullard, A. 2013 FDA drug approvals. Nat. Rev. Drug Discov., 2014, 13(2), 85-89.
[http://dx.doi.org/10.1038/nrd4239] [PMID: 24481294]
[15]
Pammolli, F.; Magazzini, L.; Riccaboni, M. The productivity crisis in pharmaceutical R&D. Nat. Rev. Drug Discov., 2011, 10(6), 428-438.
[http://dx.doi.org/10.1038/nrd3405] [PMID: 21629293]
[16]
Ashburn, T.T.; Thor, K.B. Drug repositioning: identifying and developing new uses for existing drugs. Nat. Rev. Drug Discov., 2004, 3(8), 673-683.
[http://dx.doi.org/10.1038/nrd1468] [PMID: 15286734]
[17]
Rodriguez-Esteban, R. A drug-centric view of drug development: How drugs spread from disease to disease. PLOS Comput. Biol., 2016, 12(4)e1004852
[http://dx.doi.org/10.1371/journal.pcbi.1004852] [PMID: 27124390]
[18]
Boguski, M.S.; Mandl, K.D.; Sukhatme, V.P. Drug discovery. Repurposing with a difference. Science, 2009, 324(5933), 1394-1395.
[http://dx.doi.org/10.1126/science.1169920] [PMID: 19520944]
[19]
Barrett, M.J.; Frail, D.E. Drug Repositioning: Bring New Life to Shelved Assets and Existing Drugs; Wiley, 2012, p. 498.
[http://dx.doi.org/10.1002/9781118274408]
[20]
Boolell, M.; Allen, M.J.; Ballard, S.A.; Gepi-Attee, S.; Muirhead, G.J.; Naylor, A.M.; Osterloh, I.H.; Gingell, C. Sildenafil: an orally active type 5 cyclic GMP-specific phosphodiesterase inhibitor for the treatment of penile erectile dysfunction. Int. J. Impot. Res., 1996, 8(2), 47-52.
[PMID: 8858389]
[21]
Kim, J.H.; Scialli, A.R. Thalidomide: The tragedy of birth defects and the effective treatment of disease. Toxicol. Sci., 2011, 122(1), 1-6.
[http://dx.doi.org/10.1093/toxsci/kfr088]
[22]
Kloner, R.A. Pharmacology and drug interaction effects of the phosphodiesterase 5 inhibitors: Focus on alpha-blocker interactions. Am. J. Cardiol., 2005, 96(12B), 42M-46M.
[http://dx.doi.org/10.1016/j.amjcard.2005.07.011] [PMID: 16387566]
[23]
Smith, S.W. Chiral toxicology: It’s the same thing...only different. Toxicol. Sci., 2009, 110(1), 4-30.
[24]
Palumbo, A.; Facon, T.; Sonneveld, P.; Bladè, J.; Offidani, M.; Gay, F.; Moreau, P.; Waage, A.; Spencer, A.; Ludwig, H.; Boccadoro, M.; Harousseau, J.L. Thalidomide for treatment of multiple myeloma: 10 years later. Blood, 2008, 111(8), 3968-3977.
[http://dx.doi.org/10.1182/blood-2007-10-117457] [PMID: 18245666]
[25]
Walker, S.L.; Waters, M.F.; Lockwood, D.N. The role of thalidomide in the management of erythema nodosum leprosum. Lepr. Rev., 2007, 78(3), 197-215.
[PMID: 18035771]
[26]
Lee, J.A.; Uhlik, M.T.; Moxham, C.M.; Tomandl, D.; Sall, D.J. Modern phenotypic drug discovery is a viable, neoclassic pharma strategy. J. Med. Chem., 2012, 55(10), 4527-4538.
[http://dx.doi.org/10.1021/jm201649s] [PMID: 22409666]
[27]
Zheng, W.; Thorne, N.; McKew, J.C. Phenotypic screens as a renewed approach for drug discovery. Drug Discov. Today, 2013, 18(21-22), 1067-1073.
[http://dx.doi.org/10.1016/j.drudis.2013.07.001] [PMID: 23850704]
[28]
Deftereos, S.N.; Andronis, C.; Friedla, E.J.; Persidis, A.; Persidis, A. Drug repurposing and adverse event prediction using high-throughput literature analysis. Wiley Interdiscip. Rev. Syst. Biol. Med., 2011, 3(3), 323-334.
[http://dx.doi.org/10.1002/wsbm.147] [PMID: 21416632]
[29]
Schneider, P.; Tanrikulu, Y.; Schneider, G. Self-organizing maps in drug discovery: Compound library design, scaffold-hopping, repurposing. Curr. Med. Chem., 2009, 16(3), 258-266.
[http://dx.doi.org/10.2174/092986709787002655] [PMID: 19149576]
[30]
Iorio, F.; Bosotti, R.; Scacheri, E.; Belcastro, V.; Mithbaokar, P.; Ferriero, R.; Murino, L.; Tagliaferri, R.; Brunetti-Pierri, N.; Isacchi, A.; di Bernardo, D. Discovery of drug mode of action and drug repositioning from transcriptional responses. Proc. Natl. Acad. Sci. USA, 2010, 107(33), 14621-14626.
[http://dx.doi.org/10.1073/pnas.1000138107] [PMID: 20679242]
[31]
Oprea, T.I.; Bauman, J.E.; Bologa, C.G.; Buranda, T.; Chigaev, A.; Edwards, B.S.; Jarvik, J.W.; Gresham, H.D.; Haynes, M.K.; Hjelle, B.; Hromas, R.; Hudson, L.; Mackenzie, D.A.; Muller, C.Y.; Reed, J.C.; Simons, P.C.; Smagley, Y.; Strouse, J.; Surviladze, Z.; Thompson, T.; Ursu, O.; Waller, A.; Wandinger-Ness, A.; Winter, S.S.; Wu, Y.; Young, S.M.; Larson, R.S.; Willman, C.; Sklar, L.A. Drug repurposing from an academic perspective. Drug Discov. Today Ther. Strateg., 2011, 8(3-4), 61-69.
[http://dx.doi.org/10.1016/j.ddstr.2011.10.002] [PMID: 22368688]
[32]
Ciallella, J.R.; Reaume, A.G. In vivo phenotypic screening: clinical proof of concept for a drug repositioning approach. Drug Discov. Today. Technol., 2017, 23, 45-52.
[http://dx.doi.org/10.1016/j.ddtec.2017.04.001] [PMID: 28647085]
[33]
Wang, J.Y. The capable ABL: what is its biological function? Mol. Cell. Biol., 2014, 34(7), 1188-1197.
[http://dx.doi.org/10.1128/MCB.01454-13] [PMID: 24421390]
[34]
Hantschel, O.; Superti-Furga, G. Regulation of the c-Abl and Bcr-Abl tyrosine kinases. Nat. Rev. Mol. Cell Biol., 2004, 5(1), 33-44.
[http://dx.doi.org/10.1038/nrm1280] [PMID: 14708008]
[35]
Ko, H.S.; Lee, Y.; Shin, J.H.; Karuppagounder, S.S.; Gadad, B.S.; Koleske, A.J.; Pletnikova, O.; Troncoso, J.C.; Dawson, V.L.; Dawson, T.M. Phosphorylation by the c-Abl protein tyrosine kinase inhibits parkin’s ubiquitination and protective function. Proc. Natl. Acad. Sci. USA, 2010, 107(38), 16691-16696.
[http://dx.doi.org/10.1073/pnas.1006083107] [PMID: 20823226]
[36]
Schlatterer, S.D.; Acker, C.M.; Davies, P. c-Abl in neurodegenerative disease. J. Mol. Neurosci., 2011, 45(3), 445-452.
[37]
Deininger, M.W.; Goldman, J.M.; Melo, J.V. The molecular biology of chronic myeloid leukemia. Blood, 2000, 96(10), 3343-3356.
[PMID: 11071626]
[38]
Imam, S.Z.; Zhou, Q.; Yamamoto, A.; Valente, A.J.; Ali, S.F.; Bains, M.; Roberts, J.L.; Kahle, P.J.; Clark, R.A.; Li, S. Novel regulation of parkin function through c-Abl-mediated tyrosine phosphorylation: implications for Parkinson’s disease. J. Neurosci., 2011, 31(1), 157-163.
[http://dx.doi.org/10.1523/JNEUROSCI.1833-10.2011] [PMID: 21209200]
[39]
Brahmachari, S.; Ge, P.; Lee, S.H.; Kim, D.; Karuppagounder, S.S.; Kumar, M.; Mao, X.; Shin, J.H.; Lee, Y.; Pletnikova, O.; Troncoso, J.C.; Dawson, V.L.; Dawson, T.M.; Ko, H.S. Activation of tyrosine kinase c-Abl contributes to α-synuclein-induced neurodegeneration. J. Clin. Invest., 2016, 126(8), 2970-2988.
[http://dx.doi.org/10.1172/JCI85456] [PMID: 27348587]
[40]
Lindholm, D.; Pham, D.D.; Cascone, A.; Eriksson, O.; Wennerberg, K.; Saarma, M. c-Abl inhibitors enable insights into the pathophysiology and neuroprotection in parkinson’s disease. Front. Aging Neurosci., 2016, 8, 254.
[http://dx.doi.org/10.3389/fnagi.2016.00254] [PMID: 27833551]
[41]
Tanabe, A.; Yamamura, Y.; Kasahara, J.; Morigaki, R.; Kaji, R.; Goto, S. A novel tyrosine kinase inhibitor AMN107 (nilotinib) normalizes striatal motor behaviors in a mouse model of Parkinson’s disease. Front. Cell. Neurosci., 2014, 8, 50.
[http://dx.doi.org/10.3389/fncel.2014.00050] [PMID: 24600352]
[42]
Karuppagounder, S.S.; Brahmachari, S.; Lee, Y.; Dawson, V.L.; Dawson, T.M.; Ko, H.S. The c-Abl inhibitor, nilotinib, protects dopaminergic neurons in a preclinical animal model of Parkinson’s disease. Sci. Rep., 2014, 4, 4874.
[http://dx.doi.org/10.1038/srep04874] [PMID: 24786396]
[43]
Hebron, M.L.; Lonskaya, I.; Moussa, C.E. Nilotinib reverses loss of dopamine neurons and improves motor behavior via autophagic degradation of α-synuclein in Parkinson’s disease models. Hum. Mol. Genet., 2013, 22(16), 3315-3328.
[http://dx.doi.org/10.1093/hmg/ddt192] [PMID: 23666528]
[44]
Imam, S.Z.; Trickler, W.; Kimura, S.; Binienda, Z.K.; Paule, M.G.; Slikker, W., Jr; Li, S.; Clark, R.A.; Ali, S.F. Neuroprotective efficacy of a new brain-penetrating C-Abl inhibitor in a murine Parkinson’s disease model. PLoS One, 2013, 8(5)e65129
[http://dx.doi.org/10.1371/journal.pone.0065129] [PMID: 23741470]
[45]
Zhou, Z.H.; Wu, Y.F.; Wang, X.M.; Han, Y.Z. Abl inhibitor in parkinson disease. Neurol. Sci., 2017, 38(4), 547-552.
[http://dx.doi.org/10.1007/s10072-016-2808-2]
[46]
Pagan, F.; Hebron, M.; Valadez, E.H.; Torres-Yaghi, Y.; Huang, X.; Mills, R.R.; Wilmarth, B.M.; Howard, H.; Dunn, C.; Carlson, A.; Lawler, A.; Rogers, S.L.; Falconer, R.A.; Ahn, J.; Li, Z.; Moussa, C. Nilotinib effects in parkinson’s disease and dementia with lewy bodies. J. Parkinsons Dis., 2016, 6(3), 503-517.
[http://dx.doi.org/10.3233/JPD-160867] [PMID: 27434297]
[47]
Postuma, R.B.; Berg, D.; Stern, M.; Poewe, W.; Olanow, C.W.; Oertel, W.; Obeso, J.; Marek, K.; Litvan, I.; Lang, A.E.; Halliday, G.; Goetz, C.G.; Gasser, T.; Dubois, B.; Chan, P.; Bloem, B.R.; Adler, C.H.; Deuschl, G. MDS clinical diagnostic criteria for Parkinson’s disease. Mov. Disord., 2015, 30(12), 1591-1601.
[http://dx.doi.org/10.1002/mds.26424] [PMID: 26474316]
[48]
Ferrer, I. Neuropathology and neurochemistry of nonmotor symptoms in Parkinson’s disease. Parkinsons Dis., 2011, 2011708404
[http://dx.doi.org/10.4061/2011/708404] [PMID: 21403906]
[49]
Wu, R.; Chen, H.; Ma, J.; He, Q.; Huang, Q.; Liu, Q.; Li, M.; Yuan, Z. c-Abl-p38α signaling plays an important role in MPTP-induced neuronal death. Cell Death Differ., 2016, 23(3), 542-552.
[http://dx.doi.org/10.1038/cdd.2015.135] [PMID: 26517532]
[50]
Bobela, W.; Aebischer, P.; Schneider, B.L. Alpha-synuclein as a mediator in the interplay between aging and parkinson’s disease. Biomolecules, 2015, 5(4), 2675-2700.
[http://dx.doi.org/10.3390/biom5042675] [PMID: 26501339]
[51]
Burré, J. The synaptic function of α-synuclein. J. Parkinsons Dis., 2015, 5(4), 699-713.
[http://dx.doi.org/10.3233/JPD-150642] [PMID: 26407041]
[52]
Dehay, B.; Vila, M.; Bezard, E.; Brundin, P.; Kordower, J.H. Alpha-synuclein propagation: New insights from animal models. Mov. Disord., 2016, 31(2), 161-168.
[http://dx.doi.org/10.1002/mds.26370] [PMID: 26347034]
[53]
McCann, H.; Cartwright, H.; Halliday, G.M. Neuropathology of α-synuclein propagation and braak hypothesis. Mov. Disord., 2016, 31(2), 152-160.
[http://dx.doi.org/10.1002/mds.26421] [PMID: 26340605]
[54]
Wang, T.; Hay, J.C. Alpha-synuclein toxicity in the early secretory pathway: How it drives neurodegeneration in parkinsons disease. Front. Neurosci., 2015, 9, 433.
[http://dx.doi.org/10.3389/fnins.2015.00433] [PMID: 26617485]
[55]
Peelaerts, W.; Bousset, L.; Van der Perren, A.; Moskalyuk, A.; Pulizzi, R.; Giugliano, M.; Van den Haute, C.; Melki, R.; Baekelandt, V. α-Synuclein strains cause distinct synucleinopathies after local and systemic administration. Nature, 2015, 522(7556), 340-344.
[http://dx.doi.org/10.1038/nature14547] [PMID: 26061766]
[56]
Mahul-Mellier, A.L.; Fauvet, B.; Gysbers, A.; Dikiy, I.; Oueslati, A.; Georgeon, S.; Lamontanara, A.J.; Bisquertt, A.; Eliezer, D.; Masliah, E.; Halliday, G.; Hantschel, O.; Lashuel, H.A. c-Abl phosphorylates α-synuclein and regulates its degradation: Implication for α-synuclein clearance and contribution to the pathogenesis of Parkinson’s disease. Hum. Mol. Genet., 2014, 23(11), 2858-2879.
[http://dx.doi.org/10.1093/hmg/ddt674] [PMID: 24412932]
[57]
Franco-Iborra, S.; Vila, M.; Perier, C. The parkinson disease mitochondrial hypothesis: Where are we at? Neuroscientist, 2016, 22(3), 266-277.
[http://dx.doi.org/10.1177/1073858415574600] [PMID: 25761946]
[58]
Exner, N.; Lutz, A.K.; Haass, C.; Winklhofer, K.F. Mitochondrial dysfunction in Parkinson’s disease: Molecular mechanisms and pathophysiological consequences. EMBO J., 2012, 31(14), 3038-3062.
[http://dx.doi.org/10.1038/emboj.2012.170] [PMID: 22735187]
[59]
Winklhofer, K.F. Parkin and mitochondrial quality control: toward assembling the puzzle. Trends Cell Biol., 2014, 24(6), 332-341.
[http://dx.doi.org/10.1016/j.tcb.2014.01.001] [PMID: 24485851]
[60]
Durcan, T.M.; Fon, E.A. The three 'P’s of mitophagy: PARKIN, PINK1, and post-translational modifications. Genes Dev., 2015, 29(10), 989-999.
[http://dx.doi.org/10.1101/gad.262758.115] [PMID: 25995186]
[61]
Kitada, T.; Asakawa, S.; Hattori, N.; Matsumine, H.; Yamamura, Y.; Minoshima, S.; Yokochi, M.; Mizuno, Y.; Shimizu, N. Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Nature, 1998, 392(6676), 605-608.
[http://dx.doi.org/10.1038/33416] [PMID: 9560156]
[62]
Lee, Y.; Karuppagounder, S.S.; Shin, J.H.; Lee, Y.I.; Ko, H.S.; Swing, D.; Jiang, H.; Kang, S.U.; Lee, B.D.; Kang, H.C.; Kim, D.; Tessarollo, L.; Dawson, V.L.; Dawson, T.M. Parthanatos mediates AIMP2-activated age-dependent dopaminergic neuronal loss. Nat. Neurosci., 2013, 16(10), 1392-1400.
[http://dx.doi.org/10.1038/nn.3500] [PMID: 23974709]
[63]
Stevens, D.A.; Lee, Y.; Kang, H.C.; Lee, B.D.; Lee, Y.I.; Bower, A.; Jiang, H.; Kang, S.U.; Andrabi, S.A.; Dawson, V.L.; Shin, J.H.; Dawson, T.M. Parkin loss leads to PARIS-dependent declines in mitochondrial mass and respiration. Proc. Natl. Acad. Sci. USA, 2015, 112(37), 11696-11701.
[http://dx.doi.org/10.1073/pnas.1500624112] [PMID: 26324925]
[64]
Kang, H.; Shin, J.H. Repression of rRNA transcription by PARIS contributes to Parkinson’s disease. Neurobiol. Dis., 2015, 73, 220-228.
[http://dx.doi.org/10.1016/j.nbd.2014.10.003] [PMID: 25315684]
[65]
Bibb, J.A.; Snyder, G.L.; Nishi, A.; Yan, Z.; Meijer, L.; Fienberg, A.A.; Tsai, L.H.; Kwon, Y.T.; Girault, J.A.; Czernik, A.J.; Huganir, R.L.; Hemmings, H.C., Jr; Nairn, A.C.; Greengard, P. Phosphorylation of DARPP-32 by Cdk5 modulates dopamine signalling in neurons. Nature, 1999, 402(6762), 669-671.
[http://dx.doi.org/10.1038/45251] [PMID: 10604473]
[66]
Su, L.Y.; Li, H.; Lv, L.; Feng, Y.M.; Li, G.D.; Luo, R.; Zhou, H.J.; Lei, X.G.; Ma, L.; Li, J.L.; Xu, L.; Hu, X.T.; Yao, Y.G. Melatonin attenuates MPTP-induced neurotoxicity via preventing CDK5-mediated autophagy and SNCA/α-synuclein aggregation. Autophagy, 2015, 11(10), 1745-1759.
[http://dx.doi.org/10.1080/15548627.2015.1082020] [PMID: 26292069]
[67]
Wong, A.S.; Lee, R.H.; Cheung, A.Y.; Yeung, P.K.; Chung, S.K.; Cheung, Z.H.; Ip, N.Y. Cdk5-mediated phosphorylation of endophilin B1 is required for induced autophagy in models of Parkinson’s disease. Nat. Cell Biol., 2011, 13(5), 568-579.
[http://dx.doi.org/10.1038/ncb2217] [PMID: 21499257]
[68]
Wen, Z.; Shu, Y.; Gao, C.; Wang, X.; Qi, G.; Zhang, P.; Li, M.; Shi, J.; Tian, B. CDK5-mediated phosphorylation and autophagy of RKIP regulate neuronal death in Parkinson’s disease. Neurobiol. Aging, 2014, 35(12), 2870-2880.
[http://dx.doi.org/10.1016/j.neurobiolaging.2014.05.034] [PMID: 25104559]
[69]
Alvira, D.; Ferrer, I.; Gutierrez-Cuesta, J.; Garcia-Castro, B.; Pallàs, M.; Camins, A. Activation of the calpain/cdk5/p25 pathway in the girus cinguli in Parkinson’s disease. Parkinsonism Relat. Disord., 2008, 14(4), 309-313.
[http://dx.doi.org/10.1016/j.parkreldis.2007.09.005] [PMID: 17977053]
[70]
Avraham, E.; Rott, R.; Liani, E.; Szargel, R.; Engelender, S. Phosphorylation of Parkin by the cyclin-dependent kinase 5 at the linker region modulates its ubiquitin-ligase activity and aggregation. J. Biol. Chem., 2007, 282(17), 12842-12850.
[http://dx.doi.org/10.1074/jbc.M608243200] [PMID: 17327227]
[71]
Sacchetti, P.; Carpentier, R.; Ségard, P.; Olivé-Cren, C.; Lefebvre, P. Multiple signaling pathways regulate the transcriptional activity of the orphan nuclear receptor NURR1. Nucleic Acids Res., 2006, 34(19), 5515-5527.
[http://dx.doi.org/10.1093/nar/gkl712] [PMID: 17020917]
[72]
Le, W.D.; Xu, P.; Jankovic, J.; Jiang, H.; Appel, S.H.; Smith, R.G.; Vassilatis, D.K. Mutations in NR4A2 associated with familial Parkinson disease. Nat. Genet., 2003, 33(1), 85-89.
[http://dx.doi.org/10.1038/ng1066] [PMID: 12496759]
[73]
Buervenich, S.; Carmine, A.; Arvidsson, M.; Xiang, F.; Zhang, Z.; Sydow, O.; Jönsson, E.G.; Sedvall, G.C.; Leonard, S.; Ross, R.G.; Freedman, R.; Chowdari, K.V.; Nimgaonkar, V.L.; Perlmann, T.; Anvret, M.; Olson, L. NURR1 mutations in cases of schizophrenia and manic-depressive disorder. Am. J. Med. Genet., 2000, 96(6), 808-813.
[http://dx.doi.org/10.1002/1096-8628(20001204)96:6<808:AID-AJMG23>3.0.CO;2-E] [PMID: 11121187]
[74]
Chen, Y.H.; Tsai, M.T.; Shaw, C.K.; Chen, C.H. Mutation analysis of the human NR4A2 gene, an essential gene for midbrain dopaminergic neurogenesis, in schizophrenic patients. Am. J. Med. Genet., 2001, 105(8), 753-757.
[http://dx.doi.org/10.1002/ajmg.10036] [PMID: 11803525]
[75]
Davies, M.R.; Harding, C.J.; Raines, S.; Tolley, K.; Parker, A.E.; Downey-Jones, M.; Needham, M.R. Nurr1 dependent regulation of pro-inflammatory mediators in immortalised synovial fibroblasts. J. Inflamm. (Lond.), 2005, 2, 15.
[http://dx.doi.org/10.1186/1476-9255-2-15] [PMID: 16309552]
[76]
Alavian, K.N.; Jeddi, S.; Naghipour, S.I.; Nabili, P.; Licznerski, P.; Tierney, T.S. The lifelong maintenance of mesencephalic dopaminergic neurons by Nurr1 and engrailed. J. Biomed. Sci., 2014, 21, 27.
[http://dx.doi.org/10.1186/1423-0127-21-27] [PMID: 24685177]
[77]
Jankovic, J.; Chen, S.; Le, W.D. The role of Nurr1 in the development of dopaminergic neurons and Parkinson’s disease. Prog. Neurobiol., 2005, 77(1-2), 128-138.
[http://dx.doi.org/10.1016/j.pneurobio.2005.09.001] [PMID: 16243425]
[78]
Luo, Y. The function and mechanisms of Nurr1 action in midbrain dopaminergic neurons, from development and maintenance to survival. Int. Rev. Neurobiol., 2012, 102, 1-22.
[http://dx.doi.org/10.1016/B978-0-12-386986-9.00001-6] [PMID: 22748824]
[79]
Saijo, K.; Winner, B.; Carson, C.T.; Collier, J.G.; Boyer, L.; Rosenfeld, M.G.; Gage, F.H.; Glass, C.K.A. Nurr1/CoREST pathway in microglia and astrocytes protects dopaminergic neurons from inflammation-induced death. Cell, 2009, 137(1), 47-59.
[http://dx.doi.org/10.1016/j.cell.2009.01.038] [PMID: 19345186]
[80]
Jiang, C.; Wan, X.; He, Y.; Pan, T.; Jankovic, J.; Le, W. Age-dependent dopaminergic dysfunction in Nurr1 knockout mice. Exp. Neurol., 2005, 191(1), 154-162.
[http://dx.doi.org/10.1016/j.expneurol.2004.08.035] [PMID: 15589522]
[81]
Decressac, M.; Volakakis, N.; Björklund, A.; Perlmann, T. NURR1 in Parkinson disease--from pathogenesis to therapeutic potential. Nat. Rev. Neurol., 2013, 9(11), 629-636.
[http://dx.doi.org/10.1038/nrneurol.2013.209] [PMID: 24126627]
[82]
Dong, J.; Li, S.; Mo, J.L.; Cai, H.B.; Le, W.D. Nurr1-based therapies for Parkinson’s disease. CNS Neurosci. Ther., 2016, 22(5), 351-359.
[http://dx.doi.org/10.1111/cns.12536] [PMID: 27012974]
[83]
Maxwell, M.A.; Muscat, G.E. The NR4A subgroup: immediate early response genes with pleiotropic physiological roles. Nucl. Recept. Signal., 2006, 4e002
[http://dx.doi.org/10.1621/nrs.04002] [PMID: 16604165]
[84]
Ichinose, H.; Ohye, T.; Suzuki, T.; Sumi-Ichinose, C.; Nomura, T.; Hagino, Y.; Nagatsu, T. Molecular cloning of the human Nurr1 gene: characterization of the human gene and cDNAs. Gene, 1999, 230(2), 233-239.
[http://dx.doi.org/10.1016/S0378-1119(99)00065-7] [PMID: 10216262]
[85]
Paulsen, R.F.; Granas, K.; Johnsen, H.; Rolseth, V.; Sterri, S. Three related brain nuclear receptors, NGFI-B, Nurr1, and NOR-1, as transcriptional activators. J. Mol. Neurosci., 1995, 6(4), 249-255.
[86]
Maira, M.; Martens, C.; Philips, A.; Drouin, J. Heterodimerization between members of the Nur subfamily of orphan nuclear receptors as a novel mechanism for gene activation. Mol. Cell. Biol., 1999, 19(11), 7549-7557.
[http://dx.doi.org/10.1128/MCB.19.11.7549] [PMID: 10523643]
[87]
Perlmann, T.; Jansson, L. A novel pathway for vitamin A signaling mediated by RXR heterodimerization with NGFI-B and NURR1. Genes Dev., 1995, 9(7), 769-782.
[http://dx.doi.org/10.1101/gad.9.7.769] [PMID: 7705655]
[88]
Maira, M.; Martens, C.; Batsché, E.; Gauthier, Y.; Drouin, J. Dimer-specific potentiation of NGFI-B (Nur77) transcriptional activity by the protein kinase A pathway and AF-1-dependent coactivator recruitment. Mol. Cell. Biol., 2003, 23(3), 763-776.
[http://dx.doi.org/10.1128/MCB.23.3.763-776.2003] [PMID: 12529383]
[89]
Hedrick, E.; Lee, S.O.; Kim, G.; Abdelrahim, M.; Jin, U.H.; Safe, S.; Abudayyeh, A. Nuclear receptor 4A1 (NR4A1) as a drug target for renal cell adenocarcinoma. PLoS One, 2015, 10(6)e0128308
[http://dx.doi.org/10.1371/journal.pone.0128308] [PMID: 26035713]
[90]
Inamoto, T.; Papineni, S.; Chintharlapalli, S.; Cho, S.D.; Safe, S.; Kamat, A.M. 1,1-Bis(3′-indolyl)-1-(p-chlorophenyl)methane activates the orphan nuclear receptor Nurr1 and inhibits bladder cancer growth. Mol. Cancer Ther., 2008, 7(12), 3825-3833.
[http://dx.doi.org/10.1158/1535-7163.MCT-08-0730] [PMID: 19074857]
[91]
Yoon, K.; Lee, S.O.; Cho, S.D.; Kim, K.; Khan, S.; Safe, S. Activation of nuclear TR3 (NR4A1) by a diindolylmethane analog induces apoptosis and proapoptotic genes in pancreatic cancer cells and tumors. Carcinogenesis, 2011, 32(6), 836-842.
[http://dx.doi.org/10.1093/carcin/bgr040] [PMID: 21362629]
[92]
Li, X.; Lee, S.O.; Safe, S. Structure-dependent activation of NR4A2 (Nurr1) by 1,1-bis(3′-indolyl)-1-(aromatic)methane analogs in pancreatic cancer cells. Biochem. Pharmacol., 2012, 83(10), 1445-1455.
[http://dx.doi.org/10.1016/j.bcp.2012.02.021] [PMID: 22405837]
[93]
Safe, S.; Papineni, S.; Chintharlapalli, S. Cancer chemotherapy with indole-3-carbinol, bis(3′-indolyl)methane and synthetic analogs. Cancer Lett., 2008, 269(2), 326-338.
[http://dx.doi.org/10.1016/j.canlet.2008.04.021] [PMID: 18501502]
[94]
De Miranda, B.R.; Popichak, K.A.; Hammond, S.L.; Jorgensen, B.A.; Phillips, A.T.; Safe, S.; Tjalkens, R.B. The Nurr1 activator 1,1-bis(3′-indolyl)-1-(p-chlorophenyl)methane blocks inflammatory gene expression in BV-2 microglial cells by inhibiting nuclear factor κB. Mol. Pharmacol., 2015, 87(6), 1021-1034.
[http://dx.doi.org/10.1124/mol.114.095398] [PMID: 25858541]
[95]
Hammond, S.L.; Safe, S.; Tjalkens, R.B. A novel synthetic activator of Nurr1 induces dopaminergic gene expression and protects against 6-hydroxydopamine neurotoxicity in vitro. Neurosci. Lett., 2015, 607, 83-89.
[http://dx.doi.org/10.1016/j.neulet.2015.09.015] [PMID: 26383113]
[96]
De Miranda, B.R.; Popichak, K.A.; Hammond, S.L.; Miller, J.A.; Safe, S.; Tjalkens, R.B. Novel para-phenyl substituted diindolylmethanes protect against MPTP neurotoxicity and suppress glial activation in a mouse model of Parkinson’s disease. Toxicol. Sci., 2015, 143(2), 360-373.
[http://dx.doi.org/10.1093/toxsci/kfu236]
[97]
Kim, C.H.; Han, B.S.; Moon, J.; Kim, D.J.; Shin, J.; Rajan, S.; Nguyen, Q.T.; Sohn, M.; Kim, W.G.; Han, M.; Jeong, I.; Kim, K.S.; Lee, E.H.; Tu, Y.; Naffin-Olivos, J.L.; Park, C.H.; Ringe, D.; Yoon, H.S.; Petsko, G.A.; Kim, K.S. Nuclear receptor Nurr1 agonists enhance its dual functions and improve behavioral deficits in an animal model of Parkinson’s disease. Proc. Natl. Acad. Sci. USA, 2015, 112(28), 8756-8761.
[http://dx.doi.org/10.1073/pnas.1509742112] [PMID: 26124091]
[98]
Kim, C.H.; Leblanc, P.; Kim, K.S. 4-amino-7-chloroquinoline derivatives for treating Parkinson’s disease: Implications for drug discovery. Expert Opin. Drug Discov., 2016, 11(4), 337-341.
[http://dx.doi.org/10.1517/17460441.2016.1154529] [PMID: 26924734]
[99]
Rosenthal, P.J. Antimalarial drug discovery: Old and new approaches. J. Exp. Biol., 2003, 206(Pt 21), 3735-3744.
[http://dx.doi.org/10.1242/jeb.00589] [PMID: 14506208]
[100]
Shelley, J.H. Pharmacological mechanisms of analgesic nephropathy. Kidney Int., 1978, 13(1), 15-26.
[http://dx.doi.org/10.1038/ki.1978.3] [PMID: 101707]
[101]
Qiao, S.; Tao, S.; Rojo de la Vega, M.; Park, S.L.; Vonderfecht, A.A.; Jacobs, S.L.; Zhang, D.D.; Wondrak, G.T. The antimalarial amodiaquine causes autophagic-lysosomal and proliferative blockade sensitizing human melanoma cells to starvation- and chemotherapy-induced cell death. Autophagy, 2013, 9(12), 2087-2102.
[http://dx.doi.org/10.4161/auto.26506] [PMID: 24113242]
[102]
Johnson, M. Molecular mechanisms of beta(2)-adrenergic receptor function, response, and regulation. J. Allergy Clin. Immunol., 2006, 117(1), 18-24.
[http://dx.doi.org/10.1016/j.jaci.2005.11.012] [PMID: 16387578]
[103]
Daaka, Y.; Luttrell, L.M.; Lefkowitz, R.J. Switching of the coupling of the beta2-adrenergic receptor to different G proteins by protein kinase A. Nature, 1997, 390(6655), 88-91.
[http://dx.doi.org/10.1038/36362] [PMID: 9363896]
[104]
Cude, K.J.; Montgomery, J.S.; Price, D.K.; Dixon, S.C.; Kincaid, R.L.; Kovacs, K.F.; Venzon, D.J.; Liewehr, D.J.; Johnson, M.E.; Reed, E.; Figg, W.D. The role of an androgen receptor polymorphism in the clinical outcome of patients with metastatic prostate cancer. Urol. Int., 2002, 68(1), 16-23.
[http://dx.doi.org/10.1159/000048412] [PMID: 11803263]
[105]
Roth, M.; Johnson, P.R.; Rüdiger, J.J.; King, G.G.; Ge, Q.; Burgess, J.K.; Anderson, G.; Tamm, M.; Black, J.L. Interaction between glucocorticoids and beta2 agonists on bronchial airway smooth muscle cells through synchronised cellular signalling. Lancet, 2002, 360(9342), 1293-1299.
[http://dx.doi.org/10.1016/S0140-6736(02)11319-5] [PMID: 12414205]
[106]
Peterson, L.; Ismond, K.P.; Chapman, E.; Flood, P. Potential benefits of therapeutic use of β2-adrenergic receptor agonists in neuroprotection and Parkinsonμs disease. J. Immunol. Res., 2014, •••2014103780
[http://dx.doi.org/10.1155/2014/103780] [PMID: 24741572]
[107]
Block, M.L.; Hong, J.S. Microglia and inflammation-mediated neurodegeneration: multiple triggers with a common mechanism. Prog. Neurobiol., 2005, 76(2), 77-98.
[http://dx.doi.org/10.1016/j.pneurobio.2005.06.004] [PMID: 16081203]
[108]
Langston, J.W.; Forno, L.S.; Tetrud, J.; Reeves, A.G.; Kaplan, J.A.; Karluk, D. Evidence of active nerve cell degeneration in the substantia nigra of humans years after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine exposure. Ann. Neurol., 1999, 46(4), 598-605.
[http://dx.doi.org/10.1002/1531-8249(199910)46:4<598:AID-ANA7>3.0.CO;2-F] [PMID: 10514096]
[109]
Nimmerjahn, A.; Kirchhoff, F.; Helmchen, F. Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo. Science, 2005, 308(5726), 1314-1318.
[http://dx.doi.org/10.1126/science.1110647] [PMID: 15831717]
[110]
Qian, L.; Flood, P.M. Microglial cells and Parkinson’s disease. Immunol. Res., 2008, 41(3), 155-164.
[http://dx.doi.org/10.1007/s12026-008-8018-0] [PMID: 18512160]
[111]
Tanaka, K.F.; Kashima, H.; Suzuki, H.; Ono, K.; Sawada, M. Existence of functional beta1- and beta2-adrenergic receptors on microglia. J. Neurosci. Res., 2002, 70(2), 232-237.
[http://dx.doi.org/10.1002/jnr.10399] [PMID: 12271472]
[112]
Madrigal, J.L.; Feinstein, D.L.; Dello Russo, C. Norepinephrine protects cortical neurons against microglial-induced cell death. J. Neurosci. Res., 2005, 81(3), 390-396.
[http://dx.doi.org/10.1002/jnr.20481] [PMID: 15948176]
[113]
Qian, L.; Wu, H.M.; Chen, S.H.; Zhang, D.; Ali, S.F.; Peterson, L.; Wilson, B.; Lu, R.B.; Hong, J.S.; Flood, P.M. β2-adrenergic receptor activation prevents rodent dopaminergic neurotoxicity by inhibiting microglia via a novel signaling pathway. J. Immunol., 2011, 186(7), 4443-4454.
[http://dx.doi.org/10.4049/jimmunol.1002449] [PMID: 21335487]
[114]
Mittal, S.; Bjørnevik, K. Im, D.S.; Flierl, A.; Dong, X.; Locascio, J.J.; Abo, K.M.; Long, E.; Jin, M.; Xu, B.; Xiang, Y.K.; Rochet, J.C.; Engeland, A.; Rizzu, P.; Heutink, P.; Bartels, T.; Selkoe, D.J.; Caldarone, B.J.; Glicksman, M.A.; Khurana, V.; Schüle, B.; Park, D.S.; Riise, T.; Scherzer, C.R. β2-Adrenoreceptor is a regulator of the α-synuclein gene driving risk of Parkinson’s disease. Science, 2017, 357(6354), 891-898.
[http://dx.doi.org/10.1126/science.aaf3934] [PMID: 28860381]
[115]
Schmidt, W.E.; Siegel, E.G.; Creutzfeldt, W. Glucagon-like peptide-1 but not glucagon-like peptide-2 stimulates insulin release from isolated rat pancreatic islets. Diabetologia, 1985, 28(9), 704-707.
[http://dx.doi.org/10.1007/BF00291980] [PMID: 3905480]
[116]
Deacon, C.F.; Johnsen, A.H.; Holst, J.J. Degradation of glucagon-like peptide-1 by human plasma in vitro yields an N-terminally truncated peptide that is a major endogenous metabolite in vivo. J. Clin. Endocrinol. Metab., 1995, 80(3), 952-957.
[PMID: 7883856]
[117]
Green, B.D.; Flatt, P.R.; Bailey, C.J. Dipeptidyl peptidase IV (DPP IV) inhibitors: A newly emerging drug class for the treatment of type 2 diabetes. Diab. Vasc. Dis. Res., 2006, 3(3), 159-165.
[118]
Athauda, D.; Foltynie, T. The glucagon-like peptide 1 (GLP) receptor as a therapeutic target in Parkinson’s disease: Mechanisms of action. Drug Discov. Today, 2016, 21(5), 802-818.
[http://dx.doi.org/10.1016/j.drudis.2016.01.013] [PMID: 26851597]
[119]
Cork, S.C.; Richards, J.E.; Holt, M.K.; Gribble, F.M.; Reimann, F.; Trapp, S. Distribution and characterisation of Glucagon-like peptide-1 receptor expressing cells in the mouse brain. Mol. Metab., 2015, 4(10), 718-731.
[http://dx.doi.org/10.1016/j.molmet.2015.07.008] [PMID: 26500843]
[120]
Kappe, C.; Tracy, L.M.; Patrone, C.; Iverfeldt, K.; Sjöholm, Å. GLP-1 secretion by microglial cells and decreased CNS expression in obesity. J. Neuroinflammation, 2012, 9, 276.
[http://dx.doi.org/10.1186/1742-2094-9-276] [PMID: 23259618]
[121]
Gentilella, R.; Bianchi, C.; Rossi, A.; Rotella, C.M. Exenatide: a review from pharmacology to clinical practice. Diabetes Obes. Metab., 2009, 11(6), 544-556.
[http://dx.doi.org/10.1111/j.1463-1326.2008.01018.x] [PMID: 19383034]
[122]
Drucker, D.J. Therapeutic potential of dipeptidyl peptidase IV inhibitors for the treatment of type 2 diabetes. Expert Opin. Investig. Drugs, 2003, 12(1), 87-100.
[http://dx.doi.org/10.1517/13543784.12.1.87] [PMID: 12517256]
[123]
Harkavyi, A.; Abuirmeileh, A.; Lever, R.; Kingsbury, A.E.; Biggs, C.S.; Whitton, P.S. Glucagon-like peptide 1 receptor stimulation reverses key deficits in distinct rodent models of Parkinson’s disease. J. Neuroinflammation, 2008, 5, 19.
[http://dx.doi.org/10.1186/1742-2094-5-19] [PMID: 18492290]
[124]
Li, Y.; Perry, T.; Kindy, M.S.; Harvey, B.K.; Tweedie, D.; Holloway, H.W.; Powers, K.; Shen, H.; Egan, J.M.; Sambamurti, K.; Brossi, A.; Lahiri, D.K.; Mattson, M.P.; Hoffer, B.J.; Wang, Y.; Greig, N.H. GLP-1 receptor stimulation preserves primary cortical and dopaminergic neurons in cellular and rodent models of stroke and Parkinsonism. Proc. Natl. Acad. Sci. USA, 2009, 106(4), 1285-1290.
[http://dx.doi.org/10.1073/pnas.0806720106] [PMID: 19164583]
[125]
Bertilsson, G.; Patrone, C.; Zachrisson, O.; Andersson, A.; Dannaeus, K.; Heidrich, J.; Kortesmaa, J.; Mercer, A.; Nielsen, E.; Rönnholm, H.; Wikström, L. Peptide hormone exendin-4 stimulates subventricular zone neurogenesis in the adult rodent brain and induces recovery in an animal model of Parkinson’s disease. J. Neurosci. Res., 2008, 86(2), 326-338.
[http://dx.doi.org/10.1002/jnr.21483] [PMID: 17803225]
[126]
Kim, S.; Moon, M.; Park, S. Exendin-4 protects dopaminergic neurons by inhibition of microglial activation and matrix metalloproteinase-3 expression in an animal model of Parkinson’s disease. J. Endocrinol., 2009, 202(3), 431-439.
[http://dx.doi.org/10.1677/JOE-09-0132] [PMID: 19570816]
[127]
Rampersaud, N.; Harkavyi, A.; Giordano, G.; Lever, R.; Whitton, J.; Whitton, P.S. Exendin-4 reverses biochemical and behavioral deficits in a pre-motor rodent model of Parkinson’s disease with combined noradrenergic and serotonergic lesions. Neuropeptides, 2012, 46(5), 183-193.
[http://dx.doi.org/10.1016/j.npep.2012.07.004] [PMID: 22921965]
[128]
Liu, W.; Jalewa, J.; Sharma, M.; Li, G.; Li, L.; Hölscher, C. Neuroprotective effects of lixisenatide and liraglutide in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson’s disease. Neuroscience, 2015, 303, 42-50.
[http://dx.doi.org/10.1016/j.neuroscience.2015.06.054] [PMID: 26141845]
[129]
Nassar, N.N.; Al-Shorbagy, M.Y.; Arab, H.H.; Abdallah, D.M. Saxagliptin: A novel antiparkinsonian approach. Neuropharmacology, 2015, 89, 308-317.
[http://dx.doi.org/10.1016/j.neuropharm.2014.10.007] [PMID: 25446674]
[130]
Chen, Y.; Zhang, Y.; Li, L.; Hölscher, C. Neuroprotective effects of geniposide in the MPTP mouse model of Parkinson’s disease. Eur. J. Pharmacol., 2015, 768, 21-27.
[http://dx.doi.org/10.1016/j.ejphar.2015.09.029] [PMID: 26409043]
[131]
Kang, M.Y.; Oh, T.J.; Cho, Y.M. Glucagon-like peptide-1 increases mitochondrial biogenesis and function in INS-1 rat insulinoma cells. Endocrinol. Metab. (Seoul), 2015, 30(2), 216-220.
[http://dx.doi.org/10.3803/EnM.2015.30.2.216] [PMID: 26194081]
[132]
Li, H.; Jia, Z.; Li, G.; Zhao, X.; Sun, P.; Wang, J.; Fan, Z.; Lv, G. Neuroprotective effects of exendin-4 in rat model of spinal cord injury via inhibiting mitochondrial apoptotic pathway. Int. J. Clin. Exp. Pathol., 2015, 8(5), 4837-4843.
[PMID: 26191175]
[133]
Xu, W.; Yang, Y.; Yuan, G.; Zhu, W.; Ma, D.; Hu, S. Exendin-4, a glucagon-like peptide-1 receptor agonist, reduces Alzheimer disease-associated tau hyperphosphorylation in the hippocampus of rats with type 2 diabetes. J. Investig. Med., 2015, 63(2), 267-272.
[http://dx.doi.org/10.1097/JIM.0000000000000129]
[134]
Luciani, P.; Deledda, C.; Benvenuti, S.; Cellai, I.; Squecco, R.; Monici, M.; Cialdai, F.; Luciani, G.; Danza, G.; Di Stefano, C.; Francini, F.; Peri, A. Differentiating effects of the glucagon-like peptide-1 analogue exendin-4 in a human neuronal cell model. Cell. Mol. Life Sci., 2010, 67(21), 3711-3723.
[http://dx.doi.org/10.1007/s00018-010-0398-3] [PMID: 20496097]
[135]
Athauda, D.; Foltynie, T. Insulin resistance and Parkinson’s disease: A new target for disease modification? Prog. Neurobiol., 2016, 145-146, 98-120.
[http://dx.doi.org/10.1016/j.pneurobio.2016.10.001] [PMID: 27713036]
[136]
Aviles-Olmos, I.; Dickson, J.; Kefalopoulou, Z.; Djamshidian, A.; Ell, P.; Soderlund, T.; Whitton, P.; Wyse, R.; Isaacs, T.; Lees, A.; Limousin, P.; Foltynie, T. Exenatide and the treatment of patients with Parkinson’s disease. J. Clin. Invest., 2013, 123(6), 2730-2736.
[http://dx.doi.org/10.1172/JCI68295] [PMID: 23728174]
[137]
Aviles-Olmos, I.; Dickson, J.; Kefalopoulou, Z.; Djamshidian, A.; Kahan, J.; Ell, P.; Whitton, P.; Wyse, R.; Isaacs, T.; Lees, A.; Limousin, P.; Foltynie, T. Motor and cognitive advantages persist 12 months after exenatide exposure in Parkinson’s disease. J. Parkinsons Dis., 2014, 4(3), 337-344.
[http://dx.doi.org/10.3233/JPD-140364] [PMID: 24662192]
[138]
Athauda, D.; Maclagan, K.; Skene, S.S.; Bajwa-Joseph, M.; Letchford, D.; Chowdhury, K.; Hibbert, S.; Budnik, N.; Zampedri, L.; Dickson, J.; Li, Y.; Aviles-Olmos, I.; Warner, T.T.; Limousin, P.; Lees, A.J.; Greig, N.H.; Tebbs, S.; Foltynie, T. Exenatide once weekly versus placebo in Parkinson’s disease: A randomised, double-blind, placebo-controlled trial. Lancet, 2017, 390(10103), 1664-1675.
[http://dx.doi.org/10.1016/S0140-6736(17)31585-4] [PMID: 28781108]
[139]
Braissant, O.; Foufelle, F.; Scotto, C.; Dauça, M.; Wahli, W. Differential expression of peroxisome proliferator-activated receptors (PPARs): tissue distribution of PPAR-alpha, -beta, and -gamma in the adult rat. Endocrinology, 1996, 137(1), 354-366.
[http://dx.doi.org/10.1210/endo.137.1.8536636] [PMID: 8536636]
[140]
Cullingford, T.E.; Bhakoo, K.; Peuchen, S.; Dolphin, C.T.; Patel, R.; Clark, J.B. Distribution of mRNAs encoding the peroxisome proliferator-activated receptor alpha, beta, and gamma and the retinoid X receptor alpha, beta, and gamma in rat central nervous system. J. Neurochem., 1998, 70(4), 1366-1375.
[http://dx.doi.org/10.1046/j.1471-4159.1998.70041366.x] [PMID: 9523552]
[141]
Bernardo, A.; Levi, G.; Minghetti, L. Role of the peroxisome proliferator-activated receptor-gamma (PPAR-gamma) and its natural ligand 15-deoxy-Delta12, 14-prostaglandin J2 in the regulation of microglial functions. Eur. J. Neurosci., 2000, 12(7), 2215-2223.
[http://dx.doi.org/10.1046/j.1460-9568.2000.00110.x] [PMID: 10947800]
[142]
Bernardo, A.; Minghetti, L. Regulation of glial cell functions by PPAR-gamma natural and synthetic agonists. PPAR Res., 2008, 2008864140
[http://dx.doi.org/10.1155/2008/864140] [PMID: 18464925]
[143]
Willson, T.M.; Lambert, M.H.; Kliewer, S.A. Peroxisome proliferator-activated receptor gamma and metabolic disease. Annu. Rev. Biochem., 2001, 70, 341-367.
[http://dx.doi.org/10.1146/annurev.biochem.70.1.341] [PMID: 11395411]
[144]
Breidert, T.; Callebert, J.; Heneka, M.T.; Landreth, G.; Launay, J.M.; Hirsch, E.C. Protective action of the peroxisome proliferator-activated receptor-gamma agonist pioglitazone in a mouse model of Parkinson’s disease. J. Neurochem., 2002, 82(3), 615-624.
[http://dx.doi.org/10.1046/j.1471-4159.2002.00990.x] [PMID: 12153485]
[145]
Schintu, N.; Frau, L.; Ibba, M.; Caboni, P.; Garau, A.; Carboni, E.; Carta, A.R. PPAR-gamma-mediated neuroprotection in a chronic mouse model of Parkinson’s disease. Eur. J. Neurosci., 2009, 29(5), 954-963.
[http://dx.doi.org/10.1111/j.1460-9568.2009.06657.x] [PMID: 19245367]
[146]
Dehmer, T.; Heneka, M.T.; Sastre, M.; Dichgans, J.; Schulz, J.B. Protection by pioglitazone in the MPTP model of Parkinson’s disease correlates with I kappa B alpha induction and block of NF kappa B and iNOS activation. J. Neurochem., 2004, 88(2), 494-501.
[http://dx.doi.org/10.1046/j.1471-4159.2003.02210.x] [PMID: 14690537]
[147]
Brauer, R.; Bhaskaran, K.; Chaturvedi, N.; Dexter, D.T.; Smeeth, L.; Douglas, I. Glitazone treatment and incidence of parkinson’s disease among people with diabetes: A retrospective cohort study. PLoS Med., 2015, 12(7)e1001854
[http://dx.doi.org/10.1371/journal.pmed.1001854] [PMID: 26196151]
[148]
Ghosh, A.; Tyson, T.; George, S.; Hildebrandt, E.N.; Steiner, J.A.; Madaj, Z.; Schulz, E.; Machiela, E.; McDonald, W.G.; Escobar Galvis, M.L.; Kordower, J.H.; Van Raamsdonk, J.M.; Colca, J.R.; Brundin, P. Mitochondrial pyruvate carrier regulates autophagy, inflammation, and neurodegeneration in experimental models of Parkinson’s disease. Sci. Transl. Med., 2016, 8(368)368ra174
[http://dx.doi.org/10.1126/scitranslmed.aag2210] [PMID: 27928028]
[149]
Heneka, M.T.; Landreth, G.E.; Hüll, M. Drug insight: effects mediated by peroxisome proliferator-activated receptor-gamma in CNS disorders. Nat. Clin. Pract. Neurol., 2007, 3(9), 496-504.
[http://dx.doi.org/10.1038/ncpneuro0586] [PMID: 17805244]
[150]
Straus, D.S.; Glass, C.K. Anti-inflammatory actions of PPAR ligands: New insights on cellular and molecular mechanisms. Trends Immunol., 2007, 28(12), 551-558.
[http://dx.doi.org/10.1016/j.it.2007.09.003] [PMID: 17981503]
[151]
Lehmann, J.M.; Lenhard, J.M.; Oliver, B.B.; Ringold, G.M.; Kliewer, S.A. Peroxisome proliferator-activated receptors alpha and gamma are activated by indomethacin and other non-steroidal anti-inflammatory drugs. J. Biol. Chem., 1997, 272(6), 3406-3410.
[http://dx.doi.org/10.1074/jbc.272.6.3406] [PMID: 9013583]
[152]
Esposito, E.; Di Matteo, V.; Benigno, A.; Pierucci, M.; Crescimanno, G.; Di Giovanni, G. Non-steroidal anti-inflammatory drugs in Parkinson’s disease. Exp. Neurol., 2007, 205(2), 295-312.
[http://dx.doi.org/10.1016/j.expneurol.2007.02.008] [PMID: 17433296]
[153]
Yamazaki, H.; Tanji, K.; Wakabayashi, K.; Matsuura, S.; Itoh, K. Role of the Keap1/Nrf2 pathway in neurodegenerative diseases. Pathol. Int., 2015, 65(5), 210-219.
[http://dx.doi.org/10.1111/pin.12261] [PMID: 25707882]
[154]
Rushmore, T.H.; Morton, M.R.; Pickett, C.B. The antioxidant responsive element. Activation by oxidative stress and identification of the DNA consensus sequence required for functional activity. J. Biol. Chem., 1991, 266(18), 11632-11639.
[PMID: 1646813]
[155]
Hayes, J.D.; Dinkova-Kostova, A.T. The Nrf2 regulatory network provides an interface between redox and intermediary metabolism. Trends Biochem. Sci., 2014, 39(4), 199-218.
[http://dx.doi.org/10.1016/j.tibs.2014.02.002] [PMID: 24647116]
[156]
von Otter, M.; Bergström, P.; Quattrone, A.; De Marco, E.V.; Annesi, G.; Söderkvist, P.; Wettinger, S.B.; Drozdzik, M.; Bialecka, M.; Nissbrandt, H.; Klein, C.; Nilsson, M.; Hammarsten, O.; Nilsson, S.; Zetterberg, H. Genetic associations of Nrf2-encoding NFE2L2 variants with Parkinson’s disease - a multicenter study. BMC Med. Genet., 2014, 15, 131.
[http://dx.doi.org/10.1186/s12881-014-0131-4] [PMID: 25496089]
[157]
Chen, P.C.; Vargas, M.R.; Pani, A.K.; Smeyne, R.J.; Johnson, D.A.; Kan, Y.W.; Johnson, J.A. Nrf2-mediated neuroprotection in the MPTP mouse model of Parkinson’s disease: Critical role for the astrocyte. Proc. Natl. Acad. Sci. USA, 2009, 106(8), 2933-2938.
[http://dx.doi.org/10.1073/pnas.0813361106] [PMID: 19196989]
[158]
Jazwa, A.; Rojo, A.I.; Innamorato, N.G.; Hesse, M.; Fernandez-Ruiz, J.; Cuadrado, A. Pharmacological targeting of the transcription factor Nrf2 at the basal ganglia provides disease modifying therapy for experimental parkinsonism. Antioxid. Redox Signal., 2011, 14(2), 2347-2360.
[http://dx.doi.org/10.1089/ars.2010.3731]
[159]
Kaidery, N.A.; Banerjee, R.; Yang, L.; Smirnova, N.A.; Hushpulian, D.M.; Liby, K.T.; Williams, C.R.; Yamamoto, M.; Kensler, T.W.; Ratan, R.R.; Sporn, M.B.; Beal, M.F.; Gazaryan, I.G.; Thomas, B. Targeting Nrf2-mediated gene transcription by extremely potent synthetic triterpenoids attenuate dopaminergic neurotoxicity in the MPTP mouse model of Parkinson’s disease. Antioxid. Redox Signal., 2013, 18(2), 139-157.
[http://dx.doi.org/10.1089/ars.2011.4491]
[160]
Lastres-Becker, I.; Garcia-Yague, A.J.; Scannevin, R.H.; Casarejos, M.J.; Kugler, S.; Rabano, A.; Cuadrado, A. Repurposing the NRF2 activator dimethyl fumarate as therapy against synucleinopathy in parkinson’s disease. Antioxid. Redox Signal., 2016, 25(2), 61-77.
[161]
Burton, N.C.; Kensler, T.W.; Guilarte, T.R. In vivo modulation of the Parkinsonian phenotype by Nrf2. Neurotoxicology, 2006, 27(6), 1094-1100.
[http://dx.doi.org/10.1016/j.neuro.2006.07.019] [PMID: 16959318]
[162]
García, E.; Santana-Martínez, R.; Silva-Islas, C.A.; Colín-González, A.L.; Galván-Arzate, S.; Heras, Y.; Maldonado, P.D.; Sotelo, J.; Santamaría, A. S-allyl cysteine protects against MPTP-induced striatal and nigral oxidative neurotoxicity in mice: participation of Nrf2. Free Radic. Res., 2014, 48(2), 159-167.
[http://dx.doi.org/10.3109/10715762.2013.857019] [PMID: 24147739]
[163]
Tobón-Velasco, J.C.; Vázquez-Victorio, G.; Macías-Silva, M.; Cuevas, E.; Ali, S.F.; Maldonado, P.D.; González-Trujano, M.E.; Cuadrado, A.; Pedraza-Chaverrí, J.; Santamaría, A. RETRACTED: S-allyl cysteine protects against 6-hydroxydopamine-induced neurotoxicity in the rat striatum: involvement of Nrf2 transcription factor activation and modulation of signaling kinase cascades. Free Radic. Biol. Med., 2012, 53(5), 1024-1040.
[http://dx.doi.org/10.1016/j.freeradbiomed.2012.06.040] [PMID: 22781654]
[164]
Tsou, Y.H.; Shih, C.T.; Ching, C.H.; Huang, J.Y.; Jen, C.J.; Yu, L.; Kuo, Y.M.; Wu, F.S.; Chuang, J.I. Treadmill exercise activates Nrf2 antioxidant system to protect the nigrostriatal dopaminergic neurons from MPP+ toxicity. Exp. Neurol., 2015, 263, 50-62.
[http://dx.doi.org/10.1016/j.expneurol.2014.09.021] [PMID: 25286336]
[165]
Katz, A.M. Pharmacology and mechanisms of action of calcium-channel blockers. J. Clin. Hypertens., 1986, 2(3)(Suppl.), 28S-37S.
[PMID: 3540226]
[166]
Bodi, I.; Mikala, G.; Koch, S.E.; Akhter, S.A.; Schwartz, A. The L-type calcium channel in the heart: the beat goes on. J. Clin. Invest., 2005, 115(12), 3306-3317.
[http://dx.doi.org/10.1172/JCI27167] [PMID: 16322774]
[167]
Swart, T.; Hurley, M.J. Calcium channel antagonists as disease-modifying therapy for parkinson’s disease: Therapeutic rationale and current status. CNS Drugs, 2016, 30(12), 1127-1135.
[http://dx.doi.org/10.1007/s40263-016-0393-9] [PMID: 27826740]
[168]
Biglan, K.M.; Oakes, D.; Lang, A.E.; Hauser, R.A.; Hodgeman, K.; Greco, B.; Lowell, J.; Rockhill, R.; Shoulson, I.; Venuto, C.; Young, D.; Simuni, T. Parkinson study group STEADY‐PD III Investigators.A novel design of a Phase III trial of isradipine in early Parkinson disease (STEADY-PD III). Ann. Clin. Transl. Neurol., 2017, 4(6), 360-368.
[http://dx.doi.org/10.1002/acn3.412] [PMID: 28589163]
[169]
Wang, Q.M.; Xu, Y.Y.; Liu, S.; Ma, Z.G. Isradipine attenuates MPTP-induced dopamine neuron degeneration by inhibiting up-regulation of L-type calcium channels and iron accumulation in the substantia nigra of mice. Oncotarget, 2017, 8(29), 47284-47295.
[http://dx.doi.org/10.18632/oncotarget.17618] [PMID: 28521299]
[170]
Hurley, M.J.; Brandon, B.; Gentleman, S.M.; Dexter, D.T. Parkinson’s disease is associated with altered expression of CaV1 channels and calcium-binding proteins. Brain, 2013, 136(Pt 7), 2077-2097.
[http://dx.doi.org/10.1093/brain/awt134] [PMID: 23771339]
[171]
Kuczenski, R.; Segal, D.S. Effects of methylphenidate on extracellular dopamine, serotonin, and norepinephrine: comparison with amphetamine. J. Neurochem., 1997, 68(5), 2032-2037.
[http://dx.doi.org/10.1046/j.1471-4159.1997.68052032.x] [PMID: 9109529]
[172]
Heal, D.J.; Cheetham, S.C.; Smith, S.L. The neuropharmacology of ADHD drugs in vivo: Insights on efficacy and safety. Neuropharmacology, 2009, 57(7-8), 608-618.
[http://dx.doi.org/10.1016/j.neuropharm.2009.08.020] [PMID: 19761781]
[173]
Soldani, P.; Fornai, F. The functional anatomy of noradrenergic neurons in Parkinson’s disease. Funct. Neurol., 1999, 14(2), 97-109.
[PMID: 10399622]
[174]
Devos, D.; Moreau, C.; Delval, A.; Dujardin, K.; Defebvre, L.; Bordet, R. Methylphenidate: A treatment for Parkinson’s disease? CNS Drugs, 2013, 27(1), 1-14.
[http://dx.doi.org/10.1007/s40263-012-0017-y] [PMID: 23160937]
[175]
Gainetdinov, R.R.; Jones, S.R.; Fumagalli, F.; Wightman, R.M.; Caron, M.G. Re-evaluation of the role of the dopamine transporter in dopamine system homeostasis. Brain Res. Brain Res. Rev., 1998, 26(2-3), 148-153.
[http://dx.doi.org/10.1016/S0165-0173(97)00063-5] [PMID: 9651511]
[176]
Savola, J.M.; Hill, M.; Engstrom, M.; Merivuori, H.; Wurster, S.; McGuire, S.G.; Fox, S.H.; Crossman, A.R.; Brotchie, J.M. Fipamezole (JP-1730) is a potent alpha2 adrenergic receptor antagonist that reduces levodopa-induced dyskinesia in the MPTP-lesioned primate model of Parkinson’s disease. Mov. Disord., 2003, 18(8), 872-883.
[http://dx.doi.org/10.1002/mds.10464] [PMID: 12889076]
[177]
Overtoom, C.C.; Verbaten, M.N.; Kemner, C.; Kenemans, J.L.; van Engeland, H.; Buitelaar, J.K.; van der Molen, M.W.; van der Gugten, J.; Westenberg, H.; Maes, R.A.; Koelega, H.S. Effects of methylphenidate, desipramine, and L-dopa on attention and inhibition in children with attention deficit hyperactivity disorder. Behav. Brain Res., 2003, 145(1-2), 7-15.
[http://dx.doi.org/10.1016/S0166-4328(03)00097-4] [PMID: 14529800]
[178]
Nutt, J.G.; Carter, J.H.; Carlson, N.E. Effects of methylphenidate on response to oral levodopa: a double-blind clinical trial. Arch. Neurol., 2007, 64(3), 319-323.
[http://dx.doi.org/10.1001/archneur.64.3.319] [PMID: 17353373]
[179]
Espay, A.J.; Dwivedi, A.K.; Payne, M.; Gaines, L.; Vaughan, J.E.; Maddux, B.N.; Slevin, J.T.; Gartner, M.; Sahay, A.; Revilla, F.J.; Duker, A.P.; Shukla, R. Methylphenidate for gait impairment in Parkinson disease: A randomized clinical trial. Neurology, 2011, 76(14), 1256-1262.
[http://dx.doi.org/10.1212/WNL.0b013e3182143537] [PMID: 21464430]
[180]
Devos, D.; Krystkowiak, P.; Clement, F.; Dujardin, K.; Cottencin, O.; Waucquier, N.; Ajebbar, K.; Thielemans, B.; Kroumova, M.; Duhamel, A.; Destée, A.; Bordet, R.; Defebvre, L. Improvement of gait by chronic, high doses of methylphenidate in patients with advanced Parkinson’s disease. J. Neurol. Neurosurg. Psychiatry, 2007, 78(5), 470-475.
[http://dx.doi.org/10.1136/jnnp.2006.100016] [PMID: 17098845]
[181]
Domercq, M.; Matute, C. Neuroprotection by tetracyclines. Trends Pharmacol. Sci., 2004, 25(12), 609-612.
[http://dx.doi.org/10.1016/j.tips.2004.10.001] [PMID: 15530637]
[182]
Clark, W.M.; Calcagno, F.A.; Gabler, W.L.; Smith, J.R.; Coull, B.M. Reduction of central nervous system reperfusion injury in rabbits using doxycycline treatment. Stroke, 1994, 25(7), 1411-1415.
[http://dx.doi.org/10.1161/01.STR.25.7.1411] [PMID: 8023357]
[183]
Antonio, R.C.; Ceron, C.S.; Rizzi, E.; Coelho, E.B.; Tanus-Santos, J.E.; Gerlach, R.F. Antioxidant effect of doxycycline decreases MMP activity and blood pressure in SHR. Mol. Cell. Biochem., 2014, 386(1-2), 99-105.
[http://dx.doi.org/10.1007/s11010-013-1848-7] [PMID: 24114660]
[184]
Cho, Y.; Son, H.J.; Kim, E.M.; Choi, J.H.; Kim, S.T.; Ji, I.J.; Choi, D.H.; Joh, T.H.; Kim, Y.S.; Hwang, O. Doxycycline is neuroprotective against nigral dopaminergic degeneration by a dual mechanism involving MMP-3. Neurotox. Res., 2009, 16(4), 361-371.
[http://dx.doi.org/10.1007/s12640-009-9078-1] [PMID: 19582534]
[185]
Lazzarini, M.; Martin, S.; Mitkovski, M.; Vozari, R.R.; Stühmer, W.; Bel, E.D. Doxycycline restrains glia and confers neuroprotection in a 6-OHDA Parkinson model. Glia, 2013, 61(7), 1084-1100.
[http://dx.doi.org/10.1002/glia.22496] [PMID: 23595698]
[186]
González-Lizárraga, F.; Socías, S.B.; Ávila, C.L.; Torres-Bugeau, C.M.; Barbosa, L.R.; Binolfi, A.; Sepúlveda-Díaz, J.E.; Del-Bel, E.; Fernandez, C.O.; Papy-Garcia, D.; Itri, R.; Raisman-Vozari, R.; Chehín, R.N. Repurposing doxycycline for synucleinopathies: remodelling of α-synuclein oligomers towards non-toxic parallel beta-sheet structured species. Sci. Rep., 2017, 7, 41755.
[http://dx.doi.org/10.1038/srep41755] [PMID: 28155912]
[187]
Rey, J.R.; Cervino, E.V.; Rentero, M.L.; Crespo, E.C.; Alvaro, A.O.; Casillas, M. Raloxifene: mechanism of action, effects on bone tissue, and applicability in clinical traumatology practice. Open Orthop. J., 2009, 3, 14-21.
[http://dx.doi.org/10.2174/1874325000903010014] [PMID: 19516920]
[188]
Poirier, A.A.; Côté, M.; Bourque, M.; Morissette, M.; Di Paolo, T.; Soulet, D. Neuroprotective and immunomodulatory effects of raloxifene in the myenteric plexus of a mouse model of Parkinson’s disease. Neurobiol. Aging, 2016, 48, 61-71.
[http://dx.doi.org/10.1016/j.neurobiolaging.2016.08.004] [PMID: 27644075]
[189]
Pandey, U.B.; Nichols, C.D. Human disease models in Drosophila melanogaster and the role of the fly in therapeutic drug discovery. Pharmacol. Rev., 2011, 63(2), 411-436.
[http://dx.doi.org/10.1124/pr.110.003293] [PMID: 21415126]
[190]
Feany, M.B.; Bender, W.W. A Drosophila model of Parkinson’s disease. Nature, 2000, 404(6776), 394-398.
[http://dx.doi.org/10.1038/35006074] [PMID: 10746727]
[191]
Sun, A.G.; Lin, A.Q.; Huang, S.Y.; Huo, D.; Cong, C.H. Identification of potential drugs for Parkinson’s disease based on a sub-pathway method. Int. J. Neurosci., 2016, 126(4), 318-325.
[http://dx.doi.org/10.3109/00207454.2014.986673] [PMID: 25405535]
[192]
Styczyńska-Soczka, K.; Zechini, L.; Zografos, L. Validating the Predicted Effect of Astemizole and Ketoconazole Using a Drosophila Model of Parkinson’s Disease. Assay Drug Dev. Technol., 2017, 15(3), 106-112.
[http://dx.doi.org/10.1089/adt.2017.776] [PMID: 28418693]
[193]
Richards, D.M.; Brogden, R.N.; Heel, R.C.; Speight, T.M.; Avery, G.S. Astemizole. A review of its pharmacodynamic properties and therapeutic efficacy. Drugs, 1984, 28(1), 38-61.
[http://dx.doi.org/10.2165/00003495-198428010-00003] [PMID: 6204835]
[194]
García-Ferreiro, R.E.; Kerschensteiner, D.; Major, F.; Monje, F.; Stühmer, W.; Pardo, L.A. Mechanism of block of hEag1 K+ channels by imipramine and astemizole. J. Gen. Physiol., 2004, 124(4), 301-317.
[http://dx.doi.org/10.1085/jgp.200409041] [PMID: 15365094]
[195]
Karapetyan, Y.E.; Sferrazza, G.F.; Zhou, M.; Ottenberg, G.; Spicer, T.; Chase, P.; Fallahi, M.; Hodder, P.; Weissmann, C.; Lasmézas, C.I. Unique drug screening approach for prion diseases identifies tacrolimus and astemizole as antiprion agents. Proc. Natl. Acad. Sci. USA, 2013, 110(17), 7044-7049.
[http://dx.doi.org/10.1073/pnas.1303510110] [PMID: 23576755]
[196]
Scheinfeld, N. Ketoconazole: a review of a workhorse antifungal molecule with a focus on new foam and gel formulations. Drugs Today (Barc), 2008, 44(5), 369-380.
[http://dx.doi.org/10.1358/dot.2008.44.5.1216598] [PMID: 18548138]
[197]
Halabe Bucay, A. Activation of the proopiomelanocortin gene with ketoconazole as a treatment for Parkinson’s disease: A new hypothesis. Ann. N. Y. Acad. Sci., 2008, 1144, 237-242.
[http://dx.doi.org/10.1196/annals.1418.013] [PMID: 19076380]


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 26
ISSUE: 28
Year: 2019
Page: [5340 - 5362]
Pages: 23
DOI: 10.2174/0929867325666180719144850
Price: $65

Article Metrics

PDF: 45
HTML: 3