Login Register Cart 0
Generic placeholder image

Current Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe Translate in Chinese
Review Article

Role of Autophagy in Parkinson’s Disease

Author(s): Silvia Cerri and Fabio Blandini*

Volume 26, Issue 20, 2019

Page: [3702 - 3718] Pages: 17

DOI: 10.2174/0929867325666180226094351

Price: $65

conference banner
Abstract

Autophagy is an essential catabolic mechanism that delivers misfolded proteins and damaged organelles to the lysosome for degradation. Autophagy pathways include macroautophagy, chaperone-mediated autophagy and microautophagy, each involving different mechanisms of substrate delivery to lysosome. Defects of these pathways and the resulting accumulation of protein aggregates represent a common pathobiological feature of neurodegenerative disorders such as Alzheimer, Parkinson and Huntington disease. This review provides an overview of the role of autophagy in Parkinson’s disease (PD) by summarizing the most relevant genetic and experimental evidence showing how this process can contribute to disease pathogenesis. Given lysosomes take part in the final step of the autophagic process, the role of lysosomal defects in the impairment of autophagy and their impact on disease will also be discussed. A glance on the role of non-neuronal autophagy in the pathogenesis of PD will be included. Moreover, we will examine novel pharmacological targets and therapeutic strategies that, by boosting autophagy, may be theoretically beneficial for PD. Special attention will be focused on natural products, such as phenolic compounds, that are receiving increasing consideration due to their potential efficacy associated with low toxicity. Although many efforts have been made to elucidate autophagic process, the development of new therapeutic interventions requires a deeper understanding of the mechanisms that may lead to autophagy defects in PD and should take into account the multifactorial nature of the disease as well as the phenotypic heterogeneity of PD patients.

Keywords: α-synuclein, autophagy inducers, chaperone-mediated autophagy, glucocerebrosidase, macroautophagy, Parkinson's disease.

« Previous Next »
[1]
Son, J.H.; Shim, J.H.; Kim, K.H.; Ha, J.Y.; Han, J.Y. Neuronal autophagy and neurodegenerative diseases. Exp. Mol. Med., 2012, 44(2), 89-98.
[http://dx.doi.org/10.3858/emm.2012.44.2.031] [PMID: 22257884]
[2]
Ghavami, S.; Shojaei, S.; Yeganeh, B.; Ande, S.R.; Jangamreddy, J.R.; Mehrpour, M.; Christoffersson, J.; Chaabane, W.; Moghadam, A.R.; Kashani, H.H.; Hashemi, M.; Owji, A.A.; Łos, M.J. Autophagy and apoptosis dysfunction in neurodegenerative disorders. Prog. Neurobiol., 2014, 112, 24-49.
[http://dx.doi.org/10.1016/j.pneurobio.2013.10.004] [PMID: 24211851]
[3]
Lee, S.; Sato, Y.; Nixon, R.A. Lysosomal proteolysis inhibition selectively disrupts axonal transport of degradative organelles and causes an Alzheimer’s-like axonal dystrophy. J. Neurosci., 2011, 31(21), 7817-7830.
[http://dx.doi.org/10.1523/JNEUROSCI.6412-10.2011] [PMID: 21613495]
[4]
Lang, A.E.; Lozano, A.M. Parkinson’s disease. Second of two parts. N. Engl. J. Med., 1998, 339(16), 1130-1143.
[http://dx.doi.org/10.1056/NEJM199810153391607] [PMID: 9770561]
[5]
Lang, A.E.; Lozano, A.M. Parkinson’s disease. First of two parts. N. Engl. J. Med., 1998, 339(15), 1044-1053.
[http://dx.doi.org/10.1056/NEJM199810083391506] [PMID: 9761807]
[6]
Chaudhuri, K.R.; Healy, D.G.; Schapira, A.H. National Institute for Clinical Excellence. Non-motor symptoms of Parkinson’s disease: diagnosis and management. Lancet Neurol., 2006, 5(3), 235-245.
[http://dx.doi.org/10.1016/S1474-4422(06)70373-8] [PMID: 16488379]
[7]
Schapira, A.H.V.; Chaudhuri, K.R.; Jenner, P. Non-motor features of Parkinson disease. Nat. Rev. Neurosci., 2017, 18(7), 435-450.
[http://dx.doi.org/10.1038/nrn.2017.62] [PMID: 28592904]
[8]
Zatloukal, K.; Stumptner, C.; Fuchsbichler, A.; Heid, H.; Schnoelzer, M.; Kenner, L.; Kleinert, R.; Prinz, M.; Aguzzi, A.; Denk, H. p62 Is a common component of cytoplasmic inclusions in protein aggregation diseases. Am. J. Pathol., 2002, 160(1), 255-263.
[http://dx.doi.org/10.1016/S0002-9440(10)64369-6] [PMID: 11786419]
[9]
Pollanen, M.S.; Dickson, D.W.; Bergeron, C. Pathology and biology of the Lewy body. J. Neuropathol. Exp. Neurol., 1993, 52(3), 183-191.
[http://dx.doi.org/10.1097/00005072-199305000-00001] [PMID: 7684074]
[10]
Shults, C.W. Lewy bodies. Proc. Natl. Acad. Sci. USA, 2006, 103(6), 1661-1668.
[http://dx.doi.org/10.1073/pnas.0509567103] [PMID: 16449387]
[11]
von Bohlen Und Halbach, O. Synucleins and their relationship to Parkinson’s disease. Cell Tissue Res., 2004, 318(1), 163-174.
[http://dx.doi.org/10.1007/s00441-004-0921-7] [PMID: 15503152]
[12]
Beach, T.G.; Adler, C.H.; Sue, L.I.; Vedders, L.; Lue, L.; White Iii, C.L.; Akiyama, H.; Caviness, J.N.; Shill, H.A.; Sabbagh, M.N.; Walker, D.G. Arizona Parkinson’s Disease Consortium.Multi-organ distribution of phosphorylated alpha-synuclein histopathology in subjects with Lewy body disorders. Acta Neuropathol., 2010, 119(6), 689-702.
[http://dx.doi.org/10.1007/s00401-010-0664-3] [PMID: 20306269]
[13]
Klein, C.; Westenberger, A. Genetics of Parkinson’s disease. Cold Spring Harb. Perspect. Med., 2012, 2(1), a008888.
[http://dx.doi.org/10.1101/cshperspect.a008888] [PMID: 22315721]
[14]
Schapira, A.H.; Jenner, P. Etiology and pathogenesis of Parkinson’s disease. Mov. Disord., 2011, 26(6), 1049-1055.
[http://dx.doi.org/10.1002/mds.23732] [PMID: 21626550]
[15]
Mizushima, N.; Komatsu, M. Autophagy: renovation of cells and tissues. Cell, 2011, 147(4), 728-741.
[http://dx.doi.org/10.1016/j.cell.2011.10.026] [PMID: 22078875]
[16]
Turk, V.; Stoka, V.; Vasiljeva, O.; Renko, M.; Sun, T.; Turk, B.; Turk, D. Cysteine cathepsins: from structure, function and regulation to new frontiers. Biochim. Biophys. Acta, 2012, 1824(1), 68-88.
[http://dx.doi.org/10.1016/j.bbapap.2011.10.002] [PMID: 22024571]
[17]
Kroemer, G.; Mariño, G.; Levine, B. Autophagy and the integrated stress response. Mol. Cell, 2010, 40(2), 280-293.
[http://dx.doi.org/10.1016/j.molcel.2010.09.023] [PMID: 20965422]
[18]
MacGurn, J.A. Garbage on, garbage off: new insights into plasma membrane protein quality control. Curr. Opin. Cell Biol., 2014, 29, 92-98.
[http://dx.doi.org/10.1016/j.ceb.2014.05.001] [PMID: 24908345]
[19]
Rubinsztein, D.C.; Codogno, P.; Levine, B. Autophagy modulation as a potential therapeutic target for diverse diseases. Nat. Rev. Drug Discov., 2012, 11(9), 709-730.
[http://dx.doi.org/10.1038/nrd3802] [PMID: 22935804]
[20]
Xie, Z.; Klionsky, D.J. Autophagosome formation: core machinery and adaptations. Nat. Cell Biol., 2007, 9(10), 1102-1109.
[http://dx.doi.org/10.1038/ncb1007-1102] [PMID: 17909521]
[21]
Rubinsztein, D.C.; Mariño, G.; Kroemer, G. Autophagy and aging. Cell, 2011, 146(5), 682-695.
[http://dx.doi.org/10.1016/j.cell.2011.07.030] [PMID: 21884931]
[22]
Pattingre, S.; Espert, L.; Biard-Piechaczyk, M.; Codogno, P. Regulation of macroautophagy by mTOR and Beclin 1 complexes. Biochimie, 2008, 90(2), 313-323.
[http://dx.doi.org/10.1016/j.biochi.2007.08.014] [PMID: 17928127]
[23]
Ravikumar, B.; Moreau, K.; Jahreiss, L.; Puri, C.; Rubinsztein, D.C. Plasma membrane contributes to the formation of pre-autophagosomal structures. Nat. Cell Biol., 2010, 12(8), 747-757.
[http://dx.doi.org/10.1038/ncb2078] [PMID: 20639872]
[24]
Hayashi-Nishino, M.; Fujita, N.; Noda, T.; Yamaguchi, A.; Yoshimori, T.; Yamamoto, A. A subdomain of the endoplasmic reticulum forms a cradle for autophagosome formation. Nat. Cell Biol., 2009, 11(12), 1433-1437.
[http://dx.doi.org/10.1038/ncb1991]
[25]
Ylä-Anttila, P.; Vihinen, H.; Jokitalo, E.; Eskelinen, E.L. 3D tomography reveals connections between the phagophore and endoplasmic reticulum. Autophagy, 2009, 5(8), 1180-1185.
[http://dx.doi.org/10.4161/auto.5.8.10274] [PMID: 19855179]
[26]
van der Vaart, A.; Griffith, J.; Reggiori, F. Exit from the Golgi is required for the expansion of the autophagosomal phagophore in yeast Saccharomyces cerevisiae. Mol. Biol. Cell, 2010, 21(13), 2270-2284.
[http://dx.doi.org/10.1091/mbc.e09-04-0345] [PMID: 20444982]
[27]
Yen, W.L.; Shintani, T.; Nair, U.; Cao, Y.; Richardson, B.C.; Li, Z.; Hughson, F.M.; Baba, M.; Klionsky, D.J. The conserved oligomeric Golgi complex is involved in double-membrane vesicle formation during autophagy. J. Cell Biol., 2010, 188(1), 101-114.
[http://dx.doi.org/10.1083/jcb.200904075] [PMID: 20065092]
[28]
Hailey, D.W.; Rambold, A.S.; Satpute-Krishnan, P.; Mitra, K.; Sougrat, R.; Kim, P.K.; Lippincott-Schwartz, J. Mitochondria supply membranes for autophagosome biogenesis during starvation. Cell, 2010, 141(4), 656-667.
[http://dx.doi.org/10.1016/j.cell.2010.04.009] [PMID: 20478256]
[29]
Liang, C. Negative regulation of autophagy. Cell Death Differ., 2010, 17(12), 1807-1815.
[http://dx.doi.org/10.1038/cdd.2010.115] [PMID: 20865012]
[30]
Sardiello, M.; Palmieri, M.; di Ronza, A.; Medina, D.L.; Valenza, M.; Gennarino, V.A.; Di Malta, C.; Donaudy, F.; Embrione, V.; Polishchuk, R.S.; Banfi, S.; Parenti, G.; Cattaneo, E.; Ballabio, A. A gene network regulating lysosomal biogenesis and function. Science, 2009, 325(5939), 473-477.
[http://dx.doi.org/10.1126/science.1174447] [PMID: 19556463]
[31]
Settembre, C.; Di Malta, C.; Polito, V.A.; Garcia Arencibia, M.; Vetrini, F.; Erdin, S.; Erdin, S.U.; Huynh, T.; Medina, D.; Colella, P.; Sardiello, M.; Rubinsztein, D.C.; Ballabio, A. TFEB links autophagy to lysosomal biogenesis. Science, 2011, 332(6036), 1429-1433.
[http://dx.doi.org/10.1126/science.1204592] [PMID: 21617040]
[32]
Khaminets, A.; Behl, C.; Dikic, I. Ubiquitin-Dependent And Independent Signals In Selective Autophagy. Trends Cell Biol., 2016, 26(1), 6-16.
[http://dx.doi.org/10.1016/j.tcb.2015.08.010] [PMID: 26437584]
[33]
Wurzer, B.; Zaffagnini, G.; Fracchiolla, D.; Turco, E.; Abert, C.; Romanov, J.; Martens, S. Oligomerization of p62 allows for selection of ubiquitinated cargo and isolation membrane during selective autophagy. eLife,, 2015.4e08941.
[http://dx.doi.org/10.7554/eLife.08941] [PMID: 26413874]
[34]
Dice, J.F. Peptide sequences that target cytosolic proteins for lysosomal proteolysis. Trends Biochem. Sci., 1990, 15(8), 305-309.
[http://dx.doi.org/10.1016/0968-0004(90)90019-8] [PMID: 2204156]
[35]
Cuervo, A.M. Chaperone-mediated autophagy: selectivity pays off. Trends Endocrinol. Metab., 2010, 21(3), 142-150.
[http://dx.doi.org/10.1016/j.tem.2009.10.003] [PMID: 19857975]
[36]
Cuervo, A.M.; Dice, J.F. Regulation of lamp2a levels in the lysosomal membrane. Traffic, 2000, 1(7), 570-583.
[http://dx.doi.org/10.1034/j.1600-0854.2000.010707.x] [PMID: 11208145]
[37]
Ahlberg, J.; Glaumann, H. Uptake--microautophagy--and degradation of exogenous proteins by isolated rat liver lysosomes. Effects of pH, ATP, and inhibitors of proteolysis. Exp. Mol. Pathol., 1985, 42(1), 78-88.
[http://dx.doi.org/10.1016/0014-4800(85)90020-6] [PMID: 3967751]
[38]
Farré, J.C.; Krick, R.; Subramani, S.; Thumm, M. Turnover of organelles by autophagy in yeast. Curr. Opin. Cell Biol., 2009, 21(4), 522-530.
[http://dx.doi.org/10.1016/j.ceb.2009.04.015] [PMID: 19515549]
[39]
Martinez-Vicente, M. Neuronal Mitophagy in Neurodegenerative Diseases. Front. Mol. Neurosci., 2017, 10, 64.
[http://dx.doi.org/10.3389/fnmol.2017.00064] [PMID: 28337125]
[40]
Sahu, R.; Kaushik, S.; Clement, C.C.; Cannizzo, E.S.; Scharf, B.; Follenzi, A.; Potolicchio, I.; Nieves, E.; Cuervo, A.M.; Santambrogio, L. Microautophagy of cytosolic proteins by late endosomes. Dev. Cell, 2011, 20(1), 131-139.
[http://dx.doi.org/10.1016/j.devcel.2010.12.003] [PMID: 21238931]
[41]
Kumari, U.; Tan, E.K. LRRK2 in Parkinson’s disease: genetic and clinical studies from patients. FEBS J., 2009, 276(22), 6455-6463.
[http://dx.doi.org/10.1111/j.1742-4658.2009.07344.x] [PMID: 19804413]
[42]
Plowey, E.D.; Cherra, S.J., III; Liu, Y.J.; Chu, C.T. Role of autophagy in G2019S-LRRK2-associated neurite shortening in differentiated SH-SY5Y cells. J. Neurochem., 2008, 105(3), 1048-1056.
[http://dx.doi.org/10.1111/j.1471-4159.2008.05217.x] [PMID: 18182054]
[43]
Gómez-Suaga, P.; Luzón-Toro, B.; Churamani, D.; Zhang, L.; Bloor-Young, D.; Patel, S.; Woodman, P.G.; Churchill, G.C.; Hilfiker, S. Leucine-rich repeat kinase 2 regulates autophagy through a calcium-dependent pathway involving NAADP. Hum. Mol. Genet., 2012, 21(3), 511-525.
[http://dx.doi.org/10.1093/hmg/ddr481] [PMID: 22012985]
[44]
Bang, Y.; Kim, K.S.; Seol, W.; Choi, H.J. LRRK2 interferes with aggresome formation for autophagic clearance. Mol. Cell. Neurosci., 2016, 75, 71-80.
[http://dx.doi.org/10.1016/j.mcn.2016.06.007] [PMID: 27364102]
[45]
Schapansky, J.; Nardozzi, J.D.; Felizia, F.; LaVoie, M.J. Membrane recruitment of endogenous LRRK2 precedes its potent regulation of autophagy. Hum. Mol. Genet., 2014, 23(16), 4201-4214.
[http://dx.doi.org/10.1093/hmg/ddu138] [PMID: 24682598]
[46]
Alegre-Abarrategui, J.; Christian, H.; Lufino, M.M.; Mutihac, R.; Venda, L.L.; Ansorge, O.; Wade-Martins, R. LRRK2 regulates autophagic activity and localizes to specific membrane microdomains in a novel human genomic reporter cellular model. Hum. Mol. Genet., 2009, 18(21), 4022-4034.
[http://dx.doi.org/10.1093/hmg/ddp346] [PMID: 19640926]
[47]
Bravo-San Pedro, J.M.; Niso-Santano, M.; Gómez-Sánchez, R.; Pizarro-Estrella, E.; Aiastui-Pujana, A.; Gorostidi, A.; Climent, V.; López de Maturana, R.; Sanchez-Pernaute, R.; López de Munain, A.; Fuentes, J.M.; González-Polo, R.A. The LRRK2 G2019S mutant exacerbates basal autophagy through activation of the MEK/ERK pathway. Cell. Mol. Life Sci., 2013, 70(1), 121-136.
[http://dx.doi.org/10.1007/s00018-012-1061-y] [PMID: 22773119]
[48]
Manzoni, C.; Mamais, A.; Dihanich, S.; McGoldrick, P.; Devine, M.J.; Zerle, J.; Kara, E.; Taanman, J.W.; Healy, D.G.; Marti-Masso, J.F.; Schapira, A.H.; Plun-Favreau, H.; Tooze, S.; Hardy, J.; Bandopadhyay, R.; Lewis, P.A. Pathogenic Parkinson’s disease mutations across the functional domains of LRRK2 alter the autophagic/lysosomal response to starvation. Biochem. Biophys. Res. Commun., 2013, 441(4), 862-866.
[http://dx.doi.org/10.1016/j.bbrc.2013.10.159] [PMID: 24211199]
[49]
Sánchez-Danés, A.; Richaud-Patin, Y.; Carballo-Carbajal, I.; Jiménez-Delgado, S.; Caig, C.; Mora, S.; Di Guglielmo, C.; Ezquerra, M.; Patel, B.; Giralt, A.; Canals, J.M.; Memo, M.; Alberch, J.; López-Barneo, J.; Vila, M.; Cuervo, A.M.; Tolosa, E.; Consiglio, A.; Raya, A. Disease-specific phenotypes in dopamine neurons from human iPS-based models of genetic and sporadic Parkinson’s disease. EMBO Mol. Med., 2012, 4(5), 380-395.
[http://dx.doi.org/10.1002/emmm.201200215] [PMID: 22407749]
[50]
Nguyen, H.N.; Byers, B.; Cord, B.; Shcheglovitov, A.; Byrne, J.; Gujar, P.; Kee, K.; Schüle, B.; Dolmetsch, R.E.; Langston, W.; Palmer, T.D.; Pera, R.R. LRRK2 mutant iPSC-derived DA neurons demonstrate increased susceptibility to oxidative stress. Cell Stem Cell, 2011, 8(3), 267-280.
[http://dx.doi.org/10.1016/j.stem.2011.01.013] [PMID: 21362567]
[51]
Skibinski, G.; Nakamura, K.; Cookson, M.R.; Finkbeiner, S. Mutant LRRK2 toxicity in neurons depends on LRRK2 levels and synuclein but not kinase activity or inclusion bodies. J. Neurosci., 2014, 34(2), 418-433.
[http://dx.doi.org/10.1523/JNEUROSCI.2712-13.2014] [PMID: 24403142]
[52]
Yue, Z.; Yang, X.W. Dangerous duet: LRRK2 and α-synuclein jam at CMA. Nat. Neurosci., 2013, 16(4), 375-377.
[http://dx.doi.org/10.1038/nn.3361] [PMID: 23528933]
[53]
Hsieh, C.H.; Shaltouki, A.; Gonzalez, A.E.; Bettencourt da Cruz, A.; Burbulla, L.F.; St Lawrence, E.; Schüle, B.; Krainc, D.; Palmer, T.D.; Wang, X. Functional impairment in miro degradation and mitophagy is a shared feature in familial and sporadic Parkinson’s Disease. Cell Stem Cell, 2016, 19(6), 709-724.
[http://dx.doi.org/10.1016/j.stem.2016.08.002] [PMID: 27618216]
[54]
Wang, X. Destructive cellular paths underlying familial and sporadic Parkinson disease converge on mitophagy. Autophagy, 2017, 13(11), 1998-1999.
[http://dx.doi.org/10.1080/15548627.2017.1327511] [PMID: 28598236]
[55]
Michiorri, S.; Gelmetti, V.; Giarda, E.; Lombardi, F.; Romano, F.; Marongiu, R.; Nerini-Molteni, S.; Sale, P.; Vago, R.; Arena, G.; Torosantucci, L.; Cassina, L.; Russo, M.A.; Dallapiccola, B.; Valente, E.M.; Casari, G. The Parkinson-associated protein PINK1 interacts with Beclin1 and promotes autophagy. Cell Death Differ., 2010, 17(6), 962-974.
[http://dx.doi.org/10.1038/cdd.2009.200] [PMID: 20057503]
[56]
Chu, C.T. A pivotal role for PINK1 and autophagy in mitochondrial quality control: implications for Parkinson disease. Hum. Mol. Genet., 2010, 19(R1), R28-R37.
[http://dx.doi.org/10.1093/hmg/ddq143] [PMID: 20385539]
[57]
Narendra, D.; Tanaka, A.; Suen, D.F.; Youle, R.J. Parkin is recruited selectively to impaired mitochondria and promotes their autophagy. J. Cell Biol., 2008, 183(5), 795-803.
[http://dx.doi.org/10.1083/jcb.200809125] [PMID: 19029340]
[58]
Ziviani, E.; Tao, R.N.; Whitworth, A.J. Drosophila parkin requires PINK1 for mitochondrial translocation and ubiquitinates mitofusin. Proc. Natl. Acad. Sci. USA, 2010, 107(11), 5018-5023.
[http://dx.doi.org/10.1073/pnas.0913485107] [PMID: 20194754]
[59]
Geisler, S.; Holmström, K.M.; Skujat, D.; Fiesel, F.C.; Rothfuss, O.C.; Kahle, P.J.; Springer, W. PINK1/Parkin-mediated mitophagy is dependent on VDAC1 and p62/SQSTM1. Nat. Cell Biol., 2010, 12(2), 119-131.
[http://dx.doi.org/10.1038/ncb2012] [PMID: 20098416]
[60]
Wang, X.; Winter, D.; Ashrafi, G.; Schlehe, J.; Wong, Y.L.; Selkoe, D.; Rice, S.; Steen, J.; LaVoie, M.J.; Schwarz, T.L. PINK1 and Parkin target Miro for phosphorylation and degradation to arrest mitochondrial motility. Cell, 2011, 147(4), 893-906.
[http://dx.doi.org/10.1016/j.cell.2011.10.018] [PMID: 22078885]
[61]
Haskin, J.; Szargel, R.; Shani, V.; Mekies, L.N.; Rott, R.; Lim, G.G.; Lim, K.L.; Bandopadhyay, R.; Wolosker, H.; Engelender, S. AF-6 is a positive modulator of the PINK1/parkin pathway and is deficient in Parkinson’s disease. Hum. Mol. Genet., 2013, 22(10), 2083-2096.
[http://dx.doi.org/10.1093/hmg/ddt058] [PMID: 23393160]
[62]
Bonifati, V.; Rizzu, P.; van Baren, M.J.; Schaap, O.; Breedveld, G.J.; Krieger, E.; Dekker, M.C.; Squitieri, F.; Ibanez, P.; Joosse, M.; van Dongen, J.W.; Vanacore, N.; van Swieten, J.C.; Brice, A.; Meco, G.; van Duijn, C.M.; Oostra, B.A.; Heutink, P. Mutations in the DJ-1 gene associated with autosomal recessive early-onset parkinsonism. Science, 2003, 299(5604), 256-259.
[http://dx.doi.org/10.1126/science.1077209] [PMID: 12446870]
[63]
Gao, H.; Yang, W.; Qi, Z.; Lu, L.; Duan, C.; Zhao, C.; Yang, H. DJ-1 protects dopaminergic neurons against rotenone-induced apoptosis by enhancing ERK-dependent mitophagy. J. Mol. Biol., 2012, 423(2), 232-248.
[http://dx.doi.org/10.1016/j.jmb.2012.06.034] [PMID: 22898350]
[64]
Andres-Mateos, E.; Perier, C.; Zhang, L.; Blanchard-Fillion, B.; Greco, T.M.; Thomas, B.; Ko, H.S.; Sasaki, M.; Ischiropoulos, H.; Przedborski, S.; Dawson, T.M.; Dawson, V.L. DJ-1 gene deletion reveals that DJ-1 is an atypical peroxiredoxin-like peroxidase. Proc. Natl. Acad. Sci. USA, 2007, 104(37), 14807-14812.
[http://dx.doi.org/10.1073/pnas.0703219104] [PMID: 17766438]
[65]
Krebiehl, G.; Ruckerbauer, S.; Burbulla, L.F.; Kieper, N.; Maurer, B.; Waak, J.; Wolburg, H.; Gizatullina, Z.; Gellerich, F.N.; Woitalla, D.; Riess, O.; Kahle, P.J.; Proikas-Cezanne, T.; Krüger, R. Reduced basal autophagy and impaired mitochondrial dynamics due to loss of Parkinson’s disease-associated protein DJ-1. PLoS One, 2010, 5(2), e9367.
[http://dx.doi.org/10.1371/journal.pone.0009367] [PMID: 20186336]
[66]
Thomas, K.J.; McCoy, M.K.; Blackinton, J.; Beilina, A.; van der Brug, M.; Sandebring, A.; Miller, D.; Maric, D.; Cedazo-Minguez, A.; Cookson, M.R. DJ-1 acts in parallel to the PINK1/parkin pathway to control mitochondrial function and autophagy. Hum. Mol. Genet., 2011, 20(1), 40-50.
[http://dx.doi.org/10.1093/hmg/ddq430] [PMID: 20940149]
[67]
Wang, B.; Cai, Z.; Tao, K.; Zeng, W.; Lu, F.; Yang, R.; Feng, D.; Gao, G.; Yang, Q. Essential control of mitochondrial morphology and function by chaperone-mediated autophagy through degradation of PARK7. Autophagy, 2016, 12(8), 1215-1228.
[http://dx.doi.org/10.1080/15548627.2016.1179401] [PMID: 27171370]
[68]
Gómez-Santos, C.; Ferrer, I.; Santidrián, A.F.; Barrachina, M.; Gil, J.; Ambrosio, S. Dopamine induces autophagic cell death and alpha-synuclein increase in human neuroblastoma SH-SY5Y cells. J. Neurosci. Res., 2003, 73(3), 341-350.
[http://dx.doi.org/10.1002/jnr.10663] [PMID: 12868068]
[69]
Zhu, J.H.; Horbinski, C.; Guo, F.; Watkins, S.; Uchiyama, Y.; Chu, C.T. Regulation of autophagy by extracellular signal-regulated protein kinases during 1-methyl-4-phenylpyridinium-induced cell death. Am. J. Pathol., 2007, 170(1), 75-86.
[http://dx.doi.org/10.2353/ajpath.2007.060524] [PMID: 17200184]
[70]
Yakhine-Diop, S.M.; Bravo-San Pedro, J.M.; Gómez-Sánchez, R.; Pizarro-Estrella, E.; Rodríguez-Arribas, M.; Climent, V.; Aiastui, A.; López de Munain, A.; Fuentes, J.M.; González-Polo, R.A. G2019S LRRK2 mutant fibroblasts from Parkinson’s disease patients show increased sensitivity to neurotoxin 1-methyl-4-phenylpyridinium dependent of autophagy. Toxicology, 2014, 324, 1-9.
[http://dx.doi.org/10.1016/j.tox.2014.07.001] [PMID: 25017139]
[71]
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]
[72]
Miyara, M.; Kotake, Y.; Tokunaga, W.; Sanoh, S.; Ohta, S. Mild MPP+ exposure impairs autophagic degradation through a novel lysosomal acidity-independent mechanism. J. Neurochem., 2016, 139(2), 294-308.
[http://dx.doi.org/10.1111/jnc.13700] [PMID: 27309572]
[73]
Webb, J.L.; Ravikumar, B.; Atkins, J.; Skepper, J.N.; Rubinsztein, D.C. Alpha-Synuclein is degraded by both autophagy and the proteasome. J. Biol. Chem., 2003, 278(27), 25009-25013.
[http://dx.doi.org/10.1074/jbc.M300227200] [PMID: 12719433]
[74]
Cuervo, A.M.; Stefanis, L.; Fredenburg, R.; Lansbury, P.T.; Sulzer, D. Impaired degradation of mutant alpha-synuclein by chaperone-mediated autophagy. Science, 2004, 305(5688), 1292-1295.
[http://dx.doi.org/10.1126/science.1101738] [PMID: 15333840]
[75]
Vogiatzi, T.; Xilouri, M.; Vekrellis, K.; Stefanis, L. Wild type alpha-synuclein is degraded by chaperone-mediated autophagy and macroautophagy in neuronal cells. J. Biol. Chem., 2008, 283(35), 23542-23556.
[http://dx.doi.org/10.1074/jbc.M801992200] [PMID: 18566453]
[76]
Cuervo, A.M. Chaperone-mediated autophagy: selectivity pays off. Trends Endocrinol. Metab., 2010, 21(3), 142-150.
[http://dx.doi.org/10.1016/j.tem.2009.10.003] [PMID: 19857975]
[77]
Klucken, J.; Poehler, A.M.; Ebrahimi-Fakhari, D.; Schneider, J.; Nuber, S.; Rockenstein, E.; Schlötzer-Schrehardt, U.; Hyman, B.T.; McLean, P.J.; Masliah, E.; Winkler, J. Alpha-synuclein aggregation involves a bafilomycin A 1-sensitive autophagy pathway. Autophagy, 2012, 8(5), 754-766.
[http://dx.doi.org/10.4161/auto.19371] [PMID: 22647715]
[78]
Yu, W.H.; Dorado, B.; Figueroa, H.Y.; Wang, L.; Planel, E.; Cookson, M.R.; Clark, L.N.; Duff, K.E. Metabolic activity determines efficacy of macroautophagic clearance of pathological oligomeric alpha-synuclein. Am. J. Pathol., 2009, 175(2), 736-747.
[http://dx.doi.org/10.2353/ajpath.2009.080928] [PMID: 19628769]
[79]
Su, C.J.; Feng, Y.; Liu, T.T.; Liu, X.; Bao, J.J.; Shi, A.M.; Hu, D.M.; Liu, T.; Yu, Y.L. Thioredoxin-interacting protein induced α-synuclein accumulation via inhibition of autophagic flux: Implications for Parkinson’s disease. CNS Neurosci. Ther., 2017, 23(9), 717-723.
[http://dx.doi.org/10.1111/cns.12721] [PMID: 28755477]
[80]
Xilouri, M.; Brekk, O.R.; Polissidis, A.; Chrysanthou-Piterou, M.; Kloukina, I.; Stefanis, L. Impairment of chaperone-mediated autophagy induces dopaminergic neurodegeneration in rats. Autophagy, 2016, 12(11), 2230-2247.
[http://dx.doi.org/10.1080/15548627.2016.1214777] [PMID: 27541985]
[81]
Xilouri, M.; Vogiatzi, T.; Vekrellis, K.; Park, D.; Stefanis, L. Abberant alpha-synuclein confers toxicity to neurons in part through inhibition of chaperone-mediated autophagy. PLoS One, 2009, 4(5), e5515.
[http://dx.doi.org/10.1371/journal.pone.0005515] [PMID: 19436756]
[82]
Alvarez-Erviti, L.; Rodriguez-Oroz, M.C.; Cooper, J.M.; Caballero, C.; Ferrer, I.; Obeso, J.A.; Schapira, A.H. Chaperone-mediated autophagy markers in Parkinson disease brains. Arch. Neurol., 2010, 67(12), 1464-1472.
[http://dx.doi.org/10.1001/archneurol.2010.198] [PMID: 20697033]
[83]
Wang, K.; Huang, J.; Xie, W.; Huang, L.; Zhong, C.; Chen, Z. Beclin1 and HMGB1 ameliorate the α-synuclein-mediated autophagy inhibition in PC12 cells. Diagn. Pathol., 2016, 11, 15.
[http://dx.doi.org/10.1186/s13000-016-0459-5] [PMID: 26822891]
[84]
Danzer, K.M.; Kranich, L.R.; Ruf, W.P.; Cagsal-Getkin, O.; Winslow, A.R.; Zhu, L.; Vanderburg, C.R.; McLean, P.J. Exosomal cell-to-cell transmission of alpha synuclein oligomers. Mol. Neurodegener., 2012, 7, 42.
[http://dx.doi.org/10.1186/1750-1326-7-42] [PMID: 22920859]
[85]
Poehler, A.M.; Xiang, W.; Spitzer, P.; May, V.E.; Meixner, H.; Rockenstein, E.; Chutna, O.; Outeiro, T.F.; Winkler, J.; Masliah, E.; Klucken, J. Autophagy modulates SNCA/α-synuclein release, thereby generating a hostile microenvironment. Autophagy, 2014, 10(12), 2171-2192.
[http://dx.doi.org/10.4161/auto.36436] [PMID: 25484190]
[86]
Ravikumar, B.; Sarkar, S.; Davies, J.E.; Futter, M.; Garcia-Arencibia, M.; Green-Thompson, Z.W.; Jimenez-Sanchez, M.; Korolchuk, V.I.; Lichtenberg, M.; Luo, S.; Massey, D.C.; Menzies, F.M.; Moreau, K.; Narayanan, U.; Renna, M.; Siddiqi, F.H.; Underwood, B.R.; Winslow, A.R.; Rubinsztein, D.C. Regulation of mammalian autophagy in physiology and pathophysiology. Physiol. Rev., 2010, 90(4), 1383-1435.
[http://dx.doi.org/10.1152/physrev.00030.2009] [PMID: 20959619]
[87]
Schapira, A.H. Glucocerebrosidase and Parkinson disease:Recent advances Mol. Cell. Neurosci,, 2015, 66(Pt A), 37-42.
[88]
Anheim, M.; Elbaz, A.; Lesage, S.; Durr, A.; Condroyer, C.; Viallet, F.; Pollak, P.; Bonaïti, B.; Bonaïti-Pellié, C.; Brice, A. French Parkinson Disease Genetic Group.Penetrance of Parkinson disease in glucocerebrosidase gene mutation carriers. Neurology, 2012, 78(6), 417-420.
[http://dx.doi.org/10.1212/WNL.0b013e318245f476] [PMID: 22282650]
[89]
Sidransky, E.; Samaddar, T.; Tayebi, N. Mutations in GBA are associated with familial Parkinson disease susceptibility and age at onset. Neurology, 2009, 73(17), 1424-1425.
[http://dx.doi.org/10.1212/WNL.0b013e3181b28601] [PMID: 19858467]
[90]
Dasari, S.K.; Bialik, S.; Levin-Zaidman, S.; Levin-Salomon, V.; Merrill, A.H., Jr; Futerman, A.H.; Kimchi, A. Signalome-wide RNAi screen identifies GBA1 as a positive mediator of autophagic cell death. Cell Death Differ., 2017, 24(7), 1288-1302.
[http://dx.doi.org/10.1038/cdd.2017.80] [PMID: 28574511]
[91]
Kinghorn, K.J.; Grönke, S.; Castillo-Quan, J.I.; Woodling, N.S.; Li, L.; Sirka, E.; Gegg, M.; Mills, K.; Hardy, J.; Bjedov, I.; Partridge, L. A Drosophila model of neuronopathic gaucher disease demonstrates lysosomal-autophagic defects and altered mTOR signalling and is functionally rescued by rapamycin. J. Neurosci., 2016, 36(46), 11654-11670.
[http://dx.doi.org/10.1523/JNEUROSCI.4527-15.2016] [PMID: 27852774]
[92]
Osellame, L.D.; Rahim, A.A.; Hargreaves, I.P.; Gegg, M.E.; Richard-Londt, A.; Brandner, S.; Waddington, S.N.; Schapira, A.H.; Duchen, M.R. Mitochondria and quality control defects in a mouse model of Gaucher disease--links to Parkinson’s disease. Cell Metab., 2013, 17(6), 941-953.
[http://dx.doi.org/10.1016/j.cmet.2013.04.014] [PMID: 23707074]
[93]
Rocha, E.M.; Smith, G.A.; Park, E.; Cao, H.; Graham, A.R.; Brown, E.; McLean, J.R.; Hayes, M.A.; Beagan, J.; Izen, S.C.; Perez-Torres, E.; Hallett, P.J.; Isacson, O. Sustained systemic glucocerebrosidase inhibition induces brain α-synuclein aggregation, microglia and complement C1q activation in mice. Antioxid. Redox Signal., 2015, 23(6), 550-564.
[http://dx.doi.org/10.1089/ars.2015.6307] [PMID: 26094487]
[94]
Aflaki, E.; Moaven, N.; Borger, D.K.; Lopez, G.; Westbroek, W.; Chae, J.J.; Marugan, J.; Patnaik, S.; Maniwang, E.; Gonzalez, A.N.; Sidransky, E. Lysosomal storage and impaired autophagy lead to inflammasome activation in Gaucher macrophages. Aging Cell, 2016, 15(1), 77-88.
[http://dx.doi.org/10.1111/acel.12409] [PMID: 26486234]
[95]
Mazzulli, J.R.; Xu, Y.H.; Sun, Y.; Knight, A.L.; McLean, P.J.; Caldwell, G.A.; Sidransky, E.; Grabowski, G.A.; Krainc, D. Gaucher disease glucocerebrosidase and α-synuclein form a bidirectional pathogenic loop in synucleinopathies. Cell, 2011, 146(1), 37-52.
[http://dx.doi.org/10.1016/j.cell.2011.06.001] [PMID: 21700325]
[96]
Yap, T.L.; Velayati, A.; Sidransky, E.; Lee, J.C. Membrane-bound α-synuclein interacts with glucocerebrosidase and inhibits enzyme activity. Mol. Genet. Metab., 2013, 108(1), 56-64.
[http://dx.doi.org/10.1016/j.ymgme.2012.11.010] [PMID: 23266198]
[97]
Murphy, K.E.; Gysbers, A.M.; Abbott, S.K.; Tayebi, N.; Kim, W.S.; Sidransky, E.; Cooper, A.; Garner, B.; Halliday, G.M. Reduced glucocerebrosidase is associated with increased α-synuclein in sporadic Parkinson’s disease. Brain, 2014, 137(Pt 3), 834-848.
[http://dx.doi.org/10.1093/brain/awt367] [PMID: 24477431]
[98]
Gegg, M.E.; Burke, D.; Heales, S.J.; Cooper, J.M.; Hardy, J.; Wood, N.W.; Schapira, A.H. Glucocerebrosidase deficiency in substantia nigra of parkinson disease brains. Ann. Neurol., 2012, 72(3), 455-463.
[http://dx.doi.org/10.1002/ana.23614] [PMID: 23034917]
[99]
Rocha, E.M.; Smith, G.A.; Park, E.; Cao, H.; Brown, E.; Hallett, P.; Isacson, O. Progressive decline of glucocerebrosidase in aging and Parkinson’s disease. Ann. Clin. Transl. Neurol., 2015, 2(4), 433-438.
[http://dx.doi.org/10.1002/acn3.177] [PMID: 25909088]
[100]
Schöndorf, D.C.; Aureli, M.; McAllister, F.E.; Hindley, C.J.; Mayer, F.; Schmid, B.; Sardi, S.P.; Valsecchi, M.; Hoffmann, S.; Schwarz, L.K.; Hedrich, U.; Berg, D.; Shihabuddin, L.S.; Hu, J.; Pruszak, J.; Gygi, S.P.; Sonnino, S.; Gasser, T.; Deleidi, M. iPSC-derived neurons from GBA1-associated Parkinson’s disease patients show autophagic defects and impaired calcium homeostasis. Nat. Commun., 2014, 5, 4028.
[http://dx.doi.org/10.1038/ncomms5028] [PMID: 24905578]
[101]
Fernandes, H.J.; Hartfield, E.M.; Christian, H.C.; Emmanoulidou, E.; Zheng, Y.; Booth, H.; Bogetofte, H.; Lang, C.; Ryan, B.J.; Sardi, S.P.; Badger, J.; Vowles, J.; Evetts, S.; Tofaris, G.K.; Vekrellis, K.; Talbot, K.; Hu, M.T.; James, W.; Cowley, S.A.; Wade-Martins, R. ER stress and autophagic perturbations lead to elevated extracellular α-synuclein in GBA-N370S Parkinson’s iPSC-derived dopamine neurons. Stem Cell Reports, 2016, 6(3), 342-356.
[http://dx.doi.org/10.1016/j.stemcr.2016.01.013] [PMID: 26905200]
[102]
Magalhaes, J.; Gegg, M.E.; Migdalska-Richards, A.; Doherty, M.K.; Whitfield, P.D.; Schapira, A.H. Autophagic lysosome reformation dysfunction in glucocerebrosidase deficient cells: relevance to Parkinson disease. Hum. Mol. Genet., 2016, 25(16), 3432-3445.
[http://dx.doi.org/10.1093/hmg/ddw185] [PMID: 27378698]
[103]
Du, T.T.; Wang, L.; Duan, C.L.; Lu, L.L.; Zhang, J.L.; Gao, G.; Qiu, X.B.; Wang, X.M.; Yang, H. GBA deficiency promotes SNCA/α-synuclein accumulation through autophagic inhibition by inactivated PPP2A. Autophagy, 2015, 11(10), 1803-1820.
[http://dx.doi.org/10.1080/15548627.2015.1086055] [PMID: 26378614]
[104]
Blandini, F. Neural and immune mechanisms in the pathogenesis of Parkinson’s disease. J. Neuroimmune Pharmacol., 2013, 8(1), 189-201.
[http://dx.doi.org/10.1007/s11481-013-9435-y] [PMID: 23378275]
[105]
Lee, H.J.; Suk, J.E.; Bae, E.J.; Lee, S.J. Clearance and deposition of extracellular alpha-synuclein aggregates in microglia. Biochem. Biophys. Res. Commun., 2008, 372(3), 423-428.
[http://dx.doi.org/10.1016/j.bbrc.2008.05.045] [PMID: 18492487]
[106]
Rey, N.L.; Petit, G.H.; Bousset, L.; Melki, R.; Brundin, P. Transfer of human α-synuclein from the olfactory bulb to interconnected brain regions in mice. Acta Neuropathol., 2013, 126(4), 555-573.
[http://dx.doi.org/10.1007/s00401-013-1160-3] [PMID: 23925565]
[107]
Janda, E.; Lascala, A.; Carresi, C.; Parafati, M.; Aprigliano, S.; Russo, V.; Savoia, C.; Ziviani, E.; Musolino, V.; Morani, F.; Isidoro, C.; Mollace, V. Parkinsonian toxin-induced oxidative stress inhibits basal autophagy in astrocytes via NQO2/quinone oxidoreductase 2: Implications for neuroprotection. Autophagy, 2015, 11(7), 1063-1080.
[http://dx.doi.org/10.1080/15548627.2015.1058683] [PMID: 26046590]
[108]
Alobaidi, H.; Pall, H. The role of dopamine replacement on the behavioural phenotype of Parkinson’s disease. Behav. Neurol., 2013, 26(4), 225-235.
[http://dx.doi.org/10.1155/2013/902016] [PMID: 22713412]
[109]
DeMaagd, G.; Philip, A. Parkinson’s Disease and its management: part 3: nondopaminergic and nonpharmacological treatment options. P&T, 2015, 40(10), 668-679.
[PMID: 26535023]
[110]
Valadas, J.S.; Vos, M.; Verstreken, P. Therapeutic strategies in Parkinson’s disease: what we have learned from animal models. Ann. N. Y. Acad. Sci., 2015, 1338, 16-37.
[http://dx.doi.org/10.1111/nyas.12577] [PMID: 25515068]
[111]
Jodeiri Farshbaf, M.; Ghaedi, K. Does any drug to treat cancer target mTOR and iron hemostasis in neurodegenerative disorders? Biometals, 2017, 30(1), 1-16.
[http://dx.doi.org/10.1007/s10534-016-9981-x] [PMID: 27853903]
[112]
Bové, J.; Martínez-Vicente, M.; Vila, M. Fighting neurodegeneration with rapamycin: mechanistic insights. Nat. Rev. Neurosci., 2011, 12(8), 437-452.
[http://dx.doi.org/10.1038/nrn3068] [PMID: 21772323]
[113]
Bjedov, I.; Toivonen, J.M.; Kerr, F.; Slack, C.; Jacobson, J.; Foley, A.; Partridge, L. Mechanisms of life span extension by rapamycin in the fruit fly Drosophila melanogaster. Cell Metab., 2010, 11(1), 35-46.
[http://dx.doi.org/10.1016/j.cmet.2009.11.010] [PMID: 20074526]
[114]
Harrison, D.E.; Strong, R.; Sharp, Z.D.; Nelson, J.F.; Astle, C.M.; Flurkey, K.; Nadon, N.L.; Wilkinson, J.E.; Frenkel, K.; Carter, C.S.; Pahor, M.; Javors, M.A.; Fernandez, E.; Miller, R.A. Rapamycin fed late in life extends lifespan in genetically heterogeneous mice. Nature, 2009, 460(7253), 392-395.
[http://dx.doi.org/10.1038/nature08221] [PMID: 19587680]
[115]
Tain, L.S.; Mortiboys, H.; Tao, R.N.; Ziviani, E.; Bandmann, O.; Whitworth, A.J. Rapamycin activation of 4E-BP prevents parkinsonian dopaminergic neuron loss. Nat. Neurosci., 2009, 12(9), 1129-1135.
[http://dx.doi.org/10.1038/nn.2372] [PMID: 19684592]
[116]
Pan, T.; Rawal, P.; Wu, Y.; Xie, W.; Jankovic, J.; Le, W. Rapamycin protects against rotenone-induced apoptosis through autophagy induction. Neuroscience, 2009, 164(2), 541-551.
[http://dx.doi.org/10.1016/j.neuroscience.2009.08.014] [PMID: 19682553]
[117]
Malagelada, C.; Jin, Z.H.; Jackson-Lewis, V.; Przedborski, S.; Greene, L.A. Rapamycin protects against neuron death in in vitro and in vivo models of Parkinson’s disease. J. Neurosci., 2010, 30(3), 1166-1175.
[http://dx.doi.org/10.1523/JNEUROSCI.3944-09.2010] [PMID: 20089925]
[118]
Liu, K.; Shi, N.; Sun, Y.; Zhang, T.; Sun, X. Therapeutic effects of rapamycin on MPTP-induced Parkinsonism in mice. Neurochem. Res., 2013, 38(1), 201-207.
[http://dx.doi.org/10.1007/s11064-012-0909-8] [PMID: 23117422]
[119]
Sarkar, S.; Davies, J.E.; Huang, Z.; Tunnacliffe, A.; Rubinsztein, D.C. Trehalose, a novel mTOR-independent autophagy enhancer, accelerates the clearance of mutant huntingtin and alpha-synuclein. J. Biol. Chem., 2007, 282(8), 5641-5652.
[http://dx.doi.org/10.1074/jbc.M609532200] [PMID: 17182613]
[120]
Tanji, K.; Miki, Y.; Maruyama, A.; Mimura, J.; Matsumiya, T.; Mori, F.; Imaizumi, T.; Itoh, K.; Wakabayashi, K. Trehalose intake induces chaperone molecules along with autophagy in a mouse model of Lewy body disease. Biochem. Biophys. Res. Commun., 2015, 465(4), 746-752.
[http://dx.doi.org/10.1016/j.bbrc.2015.08.076] [PMID: 26299928]
[121]
He, Q.; Koprich, J.B.; Wang, Y.; Yu, W.B.; Xiao, B.G.; Brotchie, J.M.; Wang, J. Treatment with trehalose prevents behavioral and neurochemical deficits produced in an AAV α-synuclein rat model of Parkinson’s Disease. Mol. Neurobiol., 2016, 53(4), 2258-2268.
[http://dx.doi.org/10.1007/s12035-015-9173-7] [PMID: 25972237]
[122]
Redmann, M.; Wani, W.Y.; Volpicelli-Daley, L.; Darley-Usmar, V.; Zhang, J. Trehalose does not improve neuronal survival on exposure to alpha-synuclein pre-formed fibrils. Redox Biol., 2017, 11, 429-437.
[http://dx.doi.org/10.1016/j.redox.2016.12.032] [PMID: 28068606]
[123]
Umeno, A.; Horie, M.; Murotomi, K.; Nakajima, Y.; Yoshida, Y. Antioxidative and antidiabetic effects of natural polyphenols and isoflavones. Molecules, 2016, 21(6), E708.
[http://dx.doi.org/10.3390/molecules21060708] [PMID: 27248987]
[124]
Attard, E.; Martinoli, M.G.; Cucurbitacin, E.; Cucurbitacin, E. An Experimental Lead Triterpenoid with Anticancer, Immunomodulatory and Novel Effects Against Degenerative Diseases. A Mini-Review. Curr. Top. Med. Chem., 2015, 15(17), 1708-1713.
[http://dx.doi.org/10.2174/1568026615666150427121331] [PMID: 25915611]
[125]
Ferretta, A.; Gaballo, A.; Tanzarella, P.; Piccoli, C.; Capitanio, N.; Nico, B.; Annese, T.; Di Paola, M.; Dell’aquila, C.; De Mari, M.; Ferranini, E.; Bonifati, V.; Pacelli, C.; Cocco, T. Effect of resveratrol on mitochondrial function: implications in parkin-associated familiar Parkinson’s disease. Biochim. Biophys. Acta, 2014, 1842(7), 902-915.
[http://dx.doi.org/10.1016/j.bbadis.2014.02.010] [PMID: 24582596]
[126]
Wu, Y.; Li, X.; Zhu, J.X.; Xie, W.; Le, W.; Fan, Z.; Jankovic, J.; Pan, T. Resveratrol-activated AMPK/SIRT1/autophagy in cellular models of Parkinson’s disease. Neurosignals, 2011, 19(3), 163-174.
[http://dx.doi.org/10.1159/000328516] [PMID: 21778691]
[127]
Guo, Y.J.; Dong, S.Y.; Cui, X.X.; Feng, Y.; Liu, T.; Yin, M.; Kuo, S.H.; Tan, E.K.; Zhao, W.J.; Wu, Y.C. Resveratrol alleviates MPTP-induced motor impairments and pathological changes by autophagic degradation of α-synuclein via SIRT1-deacetylated LC3. Mol. Nutr. Food Res., 2016, 60(10), 2161-2175.
[http://dx.doi.org/10.1002/mnfr.201600111] [PMID: 27296520]
[128]
Lin, T.K.; Chen, S.D.; Chuang, Y.C.; Lin, H.Y.; Huang, C.R.; Chuang, J.H.; Wang, P.W.; Huang, S.T.; Tiao, M.M.; Chen, J.B.; Liou, C.W. Resveratrol partially prevents rotenone-induced neurotoxicity in dopaminergic SH-SY5Y cells through induction of heme oxygenase-1 dependent autophagy. Int. J. Mol. Sci., 2014, 15(1), 1625-1646.
[http://dx.doi.org/10.3390/ijms15011625] [PMID: 24451142]
[129]
Anand, P.; Kunnumakkara, A.B.; Newman, R.A.; Aggarwal, B.B. Bioavailability of curcumin: problems and promises. Mol. Pharm., 2007, 4(6), 807-818.
[http://dx.doi.org/10.1021/mp700113r] [PMID: 17999464]
[130]
Aoki, H.; Takada, Y.; Kondo, S.; Sawaya, R.; Aggarwal, B.B.; Kondo, Y. Evidence that curcumin suppresses the growth of malignant gliomas in vitro and in vivo through induction of autophagy: role of Akt and extracellular signal-regulated kinase signaling pathways. Mol. Pharmacol., 2007, 72(1), 29-39.
[http://dx.doi.org/10.1124/mol.106.033167] [PMID: 17395690]
[131]
Jiang, T.F.; Zhang, Y.J.; Zhou, H.Y.; Wang, H.M.; Tian, L.P.; Liu, J.; Ding, J.Q.; Chen, S.D. Curcumin ameliorates the neurodegenerative pathology in A53T α-synuclein cell model of Parkinson’s disease through the downregulation of mTOR/p70S6K signaling and the recovery of macroautophagy. J. Neuroimmune Pharmacol., 2013, 8(1), 356-369.
[http://dx.doi.org/10.1007/s11481-012-9431-7] [PMID: 23325107]
[132]
Song, J.X.; Sun, Y.R.; Peluso, I.; Zeng, Y.; Yu, X.; Lu, J.H.; Xu, Z.; Wang, M.Z.; Liu, L.F.; Huang, Y.Y.; Chen, L.L.; Durairajan, S.S.; Zhang, H.J.; Zhou, B.; Zhang, H.Q.; Lu, A.; Ballabio, A.; Medina, D.L.; Guo, Z.; Li, M. A novel curcumin analog binds to and activates TFEB in vitro and in vivo independent of MTOR inhibition. Autophagy, 2016, 12(8), 1372-1389.
[http://dx.doi.org/10.1080/15548627.2016.1179404] [PMID: 27172265]
[133]
Kilpatrick, K.; Zeng, Y.; Hancock, T.; Segatori, L. Genetic and chemical activation of TFEB mediates clearance of aggregated α-synuclein. PLoS One, 2015, 10(3), e0120819.
[http://dx.doi.org/10.1371/journal.pone.0120819] [PMID: 25790376]
[134]
Decressac, M.; Björklund, A. TFEB: Pathogenic role and therapeutic target in Parkinson disease. Autophagy, 2013, 9(8), 1244-1246.
[http://dx.doi.org/10.4161/auto.25044] [PMID: 23715007]
[135]
Decressac, M.; Mattsson, B.; Weikop, P.; Lundblad, M.; Jakobsson, J.; Björklund, A. TFEB-mediated autophagy rescues midbrain dopamine neurons from α-synuclein toxicity. Proc. Natl. Acad. Sci. USA, 2013, 110(19), E1817-E1826.
[http://dx.doi.org/10.1073/pnas.1305623110] [PMID: 23610405]
[136]
Rigacci, S.; Miceli, C.; Nediani, C.; Berti, A.; Cascella, R.; Pantano, D.; Nardiello, P.; Luccarini, I.; Casamenti, F.; Stefani, M. Oleuropein aglycone induces autophagy via the AMPK/mTOR signalling pathway: a mechanistic insight. Oncotarget, 2015, 6(34), 35344-35357.
[http://dx.doi.org/10.18632/oncotarget.6119] [PMID: 26474288]
[137]
Achour, I.; Arel-Dubeau, A.M.; Renaud, J.; Legrand, M.; Attard, E.; Germain, M.; Martinoli, M.G. Oleuropein prevents neuronal death, mitigates mitochondrial superoxide production and modulates autophagy in a dopaminergic cellular model. Int. J. Mol. Sci., 2016, 17(8), E1293.
[http://dx.doi.org/10.3390/ijms17081293] [PMID: 27517912]
[138]
El-Horany, H.E.; El-Latif, R.N.; ElBatsh, M.M.; Emam, M.N. Ameliorative effect of quercetin on neurochemical and behavioral deficits in rotenone rat model of parkinson’s disease: modulating autophagy (Quercetin on Experimental Parkinson’s Disease). J. Biochem. Mol. Toxicol., 2016, 30(7), 360-369.
[http://dx.doi.org/10.1002/jbt.21821] [PMID: 27252111]
[139]
Ahn, T.B.; Jeon, B.S. The role of quercetin on the survival of neuron-like PC12 cells and the expression of α-synuclein. Neural Regen. Res., 2015, 10(7), 1113-1119.
[http://dx.doi.org/10.4103/1673-5374.160106] [PMID: 26330835]
[140]
Song, M.Y.; Jung, H.W.; Kang, S.Y.; Kim, K.H.; Park, Y.K. Anti-inflammatory effect of Lycii radicis in LPS-stimulated RAW 264.7 macrophages. Am. J. Chin. Med., 2014, 42(4), 891-904.
[http://dx.doi.org/10.1142/S0192415X14500566] [PMID: 25004881]
[141]
Cho, S.H.; Park, E.J.; Kim, E.O.; Choi, S.W. Study on the hypochlolesterolemic and antioxidative effects of tyramine derivatives from the root bark of Lycium chenese Miller. Nutr. Res. Pract., 2011, 5(5), 412-420.
[http://dx.doi.org/10.4162/nrp.2011.5.5.412] [PMID: 22125678]
[142]
Kim, S.J.; Lee, L.; Kim, J.H.; Lee, T.H.; Shim, I. Antidepressant-like effects of lycii radicis cortex and betaine in the forced swimming test in rats. Biomol. Ther. (Seoul), 2013, 21(1), 79-83.
[http://dx.doi.org/10.4062/biomolther.2012.072] [PMID: 24009863]
[143]
Hu, X.; Song, Q.; Li, X.; Li, D.; Zhang, Q.; Meng, W.; Zhao, Q. Neuroprotective effects of Kukoamine A on neurotoxin-induced Parkinson’s model through apoptosis inhibition and autophagy enhancement. Neuropharmacology, 2017, 117, 352-363.
[http://dx.doi.org/10.1016/j.neuropharm.2017.02.022] [PMID: 28238714]
[144]
Liu, H.Q.; Zhang, W.Y.; Luo, X.T.; Ye, Y.; Zhu, X.Z. Paeoniflorin attenuates neuroinflammation and dopaminergic neurodegeneration in the MPTP model of Parkinson’s disease by activation of adenosine A1 receptor. Br. J. Pharmacol., 2006, 148(3), 314-325.
[http://dx.doi.org/10.1038/sj.bjp.0706732] [PMID: 16582933]
[145]
Gu, X.S.; Wang, F.; Zhang, C.Y.; Mao, C.J.; Yang, J.; Yang, Y.P.; Liu, S.; Hu, L.F.; Liu, C.F. Neuroprotective Effects of Paeoniflorin on 6-OHDA-Lesioned Rat Model of Parkinson’s Disease. Neurochem. Res., 2016, 41(11), 2923-2936.
[http://dx.doi.org/10.1007/s11064-016-2011-0] [PMID: 27447883]
[146]
Khanna, R.; Benjamin, E.R.; Pellegrino, L.; Schilling, A.; Rigat, B.A.; Soska, R.; Nafar, H.; Ranes, B.E.; Feng, J.; Lun, Y.; Powe, A.C.; Palling, D.J.; Wustman, B.A.; Schiffmann, R.; Mahuran, D.J.; Lockhart, D.J.; Valenzano, K.J. The pharmacological chaperone isofagomine increases the activity of the Gaucher disease L444P mutant form of beta-glucosidase. FEBS J., 2010, 277(7), 1618-1638.
[http://dx.doi.org/10.1111/j.1742-4658.2010.07588.x] [PMID: 20148966]
[147]
Steet, R.A.; Chung, S.; Wustman, B.; Powe, A.; Do, H.; Kornfeld, S.A. The iminosugar isofagomine increases the activity of N370S mutant acid beta-glucosidase in Gaucher fibroblasts by several mechanisms. Proc. Natl. Acad. Sci. USA, 2006, 103(37), 13813-13818.
[http://dx.doi.org/10.1073/pnas.0605928103] [PMID: 16945909]
[148]
Sun, Y.; Liou, B.; Xu, Y.H.; Quinn, B.; Zhang, W.; Hamler, R.; Setchell, K.D.; Grabowski, G.A. Ex vivo and in vivo effects of isofagomine on acid β-glucosidase variants and substrate levels in Gaucher disease. J. Biol. Chem., 2012, 287(6), 4275-4287.
[http://dx.doi.org/10.1074/jbc.M111.280016] [PMID: 22167193]
[149]
Richter, F.; Fleming, S.M.; Watson, M.; Lemesre, V.; Pellegrino, L.; Ranes, B.; Zhu, C.; Mortazavi, F.; Mulligan, C.K.; Sioshansi, P.C.; Hean, S.; De La Rosa, K.; Khanna, R.; Flanagan, J.; Lockhart, D.J.; Wustman, B.A.; Clark, S.W.; Chesselet, M.F. A GCase chaperone improves motor function in a mouse model of synucleinopathy. Neurotherapeutics, 2014, 11(4), 840-856.
[http://dx.doi.org/10.1007/s13311-014-0294-x] [PMID: 25037721]
[150]
McNeill, A.; Magalhaes, J.; Shen, C.; Chau, K.Y.; Hughes, D.; Mehta, A.; Foltynie, T.; Cooper, J.M.; Abramov, A.Y.; Gegg, M.; Schapira, A.H. Ambroxol improves lysosomal biochemistry in glucocerebrosidase mutation-linked Parkinson disease cells. Brain, 2014, 137(Pt 5), 1481-1495.
[http://dx.doi.org/10.1093/brain/awu020] [PMID: 24574503]
[151]
Ambrosi, G.; Ghezzi, C.; Zangaglia, R.; Levandis, G.; Pacchetti, C.; Blandini, F. Ambroxol-induced rescue of defective glucocerebrosidase is associated with increased LIMP-2 and saposin C levels in GBA1 mutant Parkinson’s disease cells. Neurobiol. Dis., 2015, 82, 235-242.
[http://dx.doi.org/10.1016/j.nbd.2015.06.008] [PMID: 26094596]
[152]
Blanz, J.; Saftig, P. Parkinson’s disease: acid-glucocerebrosidase activity and alpha-synuclein clearance. J. Neurochem., 2016, 139(Suppl. 1), 198-215.
[http://dx.doi.org/10.1111/jnc.13517] [PMID: 26860955]
[153]
Luan, Z.; Li, L.; Higaki, K.; Nanba, E.; Suzuki, Y.; Ohno, K. The chaperone activity and toxicity of ambroxol on Gaucher cells and normal mice. Brain Dev., 2013, 35(4), 317-322.
[http://dx.doi.org/10.1016/j.braindev.2012.05.008] [PMID: 22682976]
[154]
Migdalska-Richards, A.; Daly, L.; Bezard, E.; Schapira, A.H. Ambroxol effects in glucocerebrosidase and α-synuclein transgenic mice. Ann. Neurol., 2016, 80(5), 766-775.
[http://dx.doi.org/10.1002/ana.24790] [PMID: 27859541]
[155]
Migdalska-Richards, A.; Ko, W.K.D.; Li, Q.; Bezard, E.; Schapira, A.H.V. Oral ambroxol increases brain glucocerebrosidase activity in a nonhuman primate. Synapse, 2017, 71(7)
[http://dx.doi.org/10.1002/syn.21967] [PMID: 28295625]
[156]
Suresh, S.N.; Chavalmane, A.K.; Dj, V.; Yarreiphang, H.; Rai, S.; Paul, A.; Clement, J.P.; Alladi, P.A.; Manjithaya, R. A novel autophagy modulator 6-Bio ameliorates SNCA/α-synuclein toxicity. Autophagy, 2017, 13(7), 1221-1234.
[http://dx.doi.org/10.1080/15548627.2017.1302045] [PMID: 28350199]
[157]
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(303), 42-50.
[http://dx.doi.org/10.1016/j.neuroscience.2015.06.054] [PMID: 26141845]
[158]
Liu, W.; Li, Y.; Jalewa, J.; Saunders-Wood, T.; Li, L.; Hölscher, C. Neuroprotective effects of an oxyntomodulin analogue in the MPTP mouse model of Parkinson’s disease. Eur. J. Pharmacol., 2015, 765, 284-290.
[http://dx.doi.org/10.1016/j.ejphar.2015.08.038] [PMID: 26302060]
[159]
Zhang, Y.; Chen, Y.; Li, L.; Hölscher, C. Neuroprotective effects of (Val8)GLP-1-Glu-PAL in the MPTP Parkinson’s disease mouse model. Behav. Brain Res., 2015, 293, 107-113.
[http://dx.doi.org/10.1016/j.bbr.2015.07.021] [PMID: 26187689]
[160]
Jalewa, J.; Sharma, M.K.; Hölscher, C. Novel incretin analogues improve autophagy and protect from mitochondrial stress induced by rotenone in SH-SY5Y cells. J. Neurochem., 2016, 139(1), 55-67.
[http://dx.doi.org/10.1111/jnc.13736] [PMID: 27412483]

Rights & Permissions Print Cite
Article Metrics
172
39
1
2
Wayfinder Image
© 2024 Bentham Science Publishers | Privacy Policy