Autophagy pathways and key drug targets in Parkinson's disease

Yaoxue Xuebao

Volumn 51, Issue 1, 2016, Pages 9-17

  Ouyang, Liang ^a   Zhang, Lan ^a   Liu, Bo ^a  

^a SICHUAN UNIVERSITY   (China)

Author keywords

A synuclein; Autophagy; Mitophagy; Parkinson's disease; Parkinson's disease therapy

Indexed keywords

ALPHA SYNUCLEIN; PARKIN; PEPTIDES AND PROTEINS; PROTEIN PINK1; UNCLASSIFIED DRUG; PROTEIN KINASE; PTEN-INDUCED PUTATIVE KINASE; UBIQUITIN PROTEIN LIGASE;

ARTICLE; AUTOPHAGY; DRUG TARGETING; HUMAN; NONHUMAN; PARKINSON DISEASE; PATHOGENESIS; ANIMAL; METABOLISM; PATHOPHYSIOLOGY;

ALPHA-SYNUCLEIN; ANIMALS; AUTOPHAGY; HUMANS; PARKINSON DISEASE; PROTEIN KINASES; UBIQUITIN-PROTEIN LIGASES;

EID: 84970024911     PISSN: 05134870     EISSN: None     Source Type: Journal    
DOI: 10.16438/j.0513-4870.2015-0706     Document Type: Article

References (94)

1. Damier P, Hirsch EC, Agid Y, et al. The substantia nigra of the human brain. II. Patterns of loss of dopamine-containing neurons in Parkinson's disease [J]. Brain, 1999, 122: 1437-1448.
2. Shulman JM, De Jager PL, Feany MB. Parkinson's disease: genetics and pathogenesis [J]. Annu Rev Pathol, 2011, 6: 193-222.
3. Fahn S. Description of Parkinson's disease as a clinical syndrome [J]. Ann NY Acad Sci, 2003, 991: 1-14.
4. Driver-Dunckley E, Adler CH, Hentz JG, et al. Olfactory dysfunction in incidental Lewy body disease and Parkinson's disease [J]. Parkinsonism Relat Disord, 2014, 20: 1260-1262.
5. Dorsey ER, Constantinescu R, Thompson JP, et al. Projected number of people with Parkinson disease in the most populous nations, 2005 through 2030 [J]. Neurology, 2007, 68: 384-386.
6. Thomson Reuters. Disease briefing: Parkinson's disease[J]. J Int Pharm Res. 2015, 42: 338-345.
7. Huang J, Klionsky DJ. Autophagy and human disease [J]. Cell Cycle, 2007, 6: 1837-1849.
8. Majeski AE, Dice JF. Mechanisms of chaperone-mediated autophagy [J]. Int J Biochem Cell Biol, 2004, 36: 2435-2444.
9. Mercer CA, Kaliappan A, Dennis PB. A novel, human Atg13 binding protein, Atg101, interacts with ULK1 and is essential for macroautophagy [J]. Autophagy, 2009, 5: 649-662.
10. Jung CH, Jun CB, Ro SH, et al. ULK-Atg13-FIP200 complexes mediate mTOR signaling to the autophagy machinery [J]. Mol Biol Cell, 2009, 20: 1992-2003.
11. Geng J, Klionsky DJ. The Atg8 and Atg12 ubiquitin-like conjugation systems in macroautophagy. 'Protein modifications: beyond the usual suspects' review series [J]. EMBO Rep, 2008, 9: 859-864.
12. Mizushima N, Kuma A, Kobayashi Y, et al. Mouse Apg16L, a novel WD-repeat protein, targets to the autophagic isolation membrane with the Apg12-Apg5 conjugate [J]. J Cell Sci, 2003, 116: 1679-1688.
13. Yuan HX, Russell RC, Guan KL. Regulation of PIK3C3/VPS34 complexes by mTOR in nutrient stress-induced autophagy [J]. Autophagy, 2013, 9: 1983-1995.
14. Suzuki SW, Yamamoto H, Oikawa Y, et al. Atg13 HORMA domain recruits Atg9 vesicles during autophagosome formation [J]. Proc Natl Acad Sci USA, 2015, 112:3350-3355.
15. Kim J, Kundu M, Viollet B, et al. AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1 [J]. Nat Cell Biol, 2011, 13: 132-141.
16. Klionsky DJ, Baehrecke EH, Brumell JH, et al. A comprehensive glossary of autophagy-related molecules and processes (2nd ed) [J]. Autophagy, 2011, 7: 1273-1294.
17. Zavodszky E, Seaman MN, Moreau K, et al. Mutation in VPS35 associated with Parkinson's disease impairs WASH complex association and inhibits autophagy [J]. Nat Commun, 2014, 5:3828.
18. Ahmed I, Liang Y, Schools S, et al. Development and characterization of a new Parkinson's disease model resulting from impaired autophagy [J]. J Neurosci, 2012, 32: 16503-16509.
19. Shen YF, Tang Y, Zhang XJ, et al. Adaptive changes in autophagy after UPS impairment in Parkinson's disease [J]. Acta Pharmacol Sin, 2013, 34: 667-673.
20. Manzoni C, Marnais A, Dihanich S, et al. Pathogenic Parkinson's disease mutations across the functional domains of LRRK2 alter the autophagic/lysosomal response to starvation [J]. Biochem Biophys Res Commun, 2013, 441: 862-866.
21. Li J, Li S, Zhang L, et al. Deconvoluting the complexity of autophagy and Parkinson's disease for potential therapeutic purpose [J]. Oncotarget, 2015, 6:40480-40495.
22. Auluck PK, Caraveo G, Lindquist S. α-Synuclein: membrane interactions and toxicity in Parkinson's disease [J]. Annu Rev Cell Dev Biol, 2010, 26: 211-233.
23. Polymeropoulos MH, Lavedan C, Leroy E, et al. Mutation in the α-synuclein gene identified in families with Parkinson's disease [J]. Science, 1997, 276: 2045-2047.
24. Krüger R, Kuhn W, Müller T, et al. Ala30Pro mutation in the gene encoding α-synuclein in Parkinson's disease [J]. Nat Genet, 1998, 18:106-108.
25. Zarranz JJ, Alegre J, Gómez-Esteban JC, et al. The new mutation, E46K, of α-synuclein causes Parkinson and Lewy body dementia [J]. Ann Neurol, 2004, 55: 164-173.
26. Chartier-Harlin MC, Kachergus J, Roumier C, et al. α-Synuclein locus duplication as a cause of familial Parkinson's disease [J]. Lancet, 2004, 364: 1167-1169.
27. Singleton AB, Farrer M, Johnson J, et al. α-Synuclein locus triplication causes Parkinson's disease [J]. Science, 2003, 302: 841.
28. Maraganore DM, de Andrade M, Elbaz A, et al. Collaborative analysis of α-synuclein gene promoter variability and Parkinson disease [J]. JAMA, 2006, 296: 661-670.
29. Bartels T, Choi JG, Selkoe DJ. α-Synuclein occurs physiologically as a helically folded tetramer that resists aggregation [J]. Nature, 2011, 477: 107-110.
30. Appel-Cresswell S, Vilarino-Guell C, Encarnacion M, et al. Alpha-synuclein p.H50Q, a novel pathogenic mutation for Parkinson's disease [J]. Mov Disord, 2013, 28: 811-813.
31. Ebrahimi-Fakhari D, Cantuti-Castelvetri I, Fan Z, et al. Distinct roles in vivo for the ubiquitin-proteasome system and the autophagy-lysosomal pathway in the degradation of α-synuclein [J]. JNeurosci, 2011, 31: 14508-14520.
32. Webb JL, Ravikumar B, Atkins J, et al. α-Synuclein is degraded by both autophagy and the proteasome [J]. J Biol Chem, 2003, 278:25009-25013.
33. Cuervo AM, Stefanis L, Fredenburg R, et al. Impaired degradation of mutant α-synuclein by chaperone-mediated autophagy [J]. Science, 2004, 305: 1292-1295.
34. Stefanis L, Larsen KE, Rideout HJ, et al. Expression of A53T mutant but not wild-type α-synuclein in PC12 cells induces alterations of the ubiquitin-dependent degradation system, loss of dopamine release, and autophagic cell death [J]. J Neurosci, 2001, 21: 9549-9560.
35. Xilouri M, Vogiatzi T, Vekrellis K, et al. Alpha-synuclein degradation by autophagic pathways: a potential key to Parkinson's disease pathogenesis [J]. Autophagy, 2008, 4: 917-919.
36. Ebrahimi-Fakhari D, McLean PJ, Unni VK. Alpha-synuclein's degradation in vivo: opening a new (cranial) window on the roles of degradation pathways in Parkinson disease [J]. Autophagy, 2012, 8:281-283.
37. Lynch-Day MA, Mao K, Wang K, et al. The role of autophagy in Parkinson's disease [J]. Cold Spring Harb Perspect Med, 2012, 2: a009357.
38. Jiang TF, Zhang YJ, Zhou HY, et al. 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]. J Neuroimmune Pharmacol, 2013, 8: 356-369.
39. Yan JQ, Yuan YH, Gao YN, et al. Overexpression of human E46K mutant α-synuclein impairs macroautophagy via inactivation of JNK1-Bcl-2 pathway [J]. Mol Neurobiol, 2014, 50:685-701.
40. Chen L, Xie Z, Turkson S, et al. A53T human α-synuclein overexpression in transgenic mice induces pervasive mitochondria macroautophagy defects preceding dopamine neuron degeneration [J]. JNeurosci, 2015, 35: 890-905.
41. Bendor JT, Logan TP, Edwards RH. The function of α-synuclein [J]. Neuron, 2013, 79: 1044-1066.
42. McBride HM, Neuspiel M, Wasiak S. Mitochondria: more than just a powerhouse [J]. Curr Biol, 2006, 16: R551-R560.
43. Celsi F, Pizzo P, Brini M, et al. Mitochondria, calcium and cell death: a deadly triad in neurodegeneration [J]. Biochim Biophys Acta, 2009, 1787: 335-344.
44. Wallace DC A mitochondrial paradigm of metabolic and degenerative diseases, aging, and cancer: a dawn for evolutionary medicine [J]. Annu Rev Genet, 2005, 39: 359-407.
45. Hedrich K, Marder K, Harris J, et al. Evaluation of 50 probands with earlyonset Parkinson's disease for Parkin mutations [J]. Neurology, 2002, 58: 1239-1246.
46. Hattori N, Kitada T, Matsumine H, et al. Molecular genetic analysis of a novel Parkin gene in Japanese families with autosomal recessive juvenile parkinsonism: evidence for variable homozygous deletions in the Parkin gene in affected individuals [J]. Ann Neurol, 1998, 44: 935-941.
47. Valente EM, Bentivoglio AR, Dixon PH, et al. Localization of a novel locus for autosomal recessive early-onset parkinsonism, PARK6, on human chromosome 1p35-p36 [J]. Am J Hum Genet, 2001, 68: 895-900.
48. Shimura H, Hattori N, Kubo S, et al. Familial Parkinson disease gene product, parkin, is an ubiquitin-protein ligase [J]. Nat Genet, 2000, 25: 302-305.
49. Li Y, Tomiyama H, Sato K, et al. Clinicogenetic study of PINK1 mutations in autosomal recessive early-onset parkinsonism [J]. Neurology, 2005, 64: 1955-1957.
50. Rohé CF, Montagna P, Breedveld G, et al. Homozygous PINK1 C-terminus mutation causing early-onset parkinsonism [J]. Ann Neurol, 2004, 56: 427-431.
51. Kann M, Jacobs H, Mohrmann K, et al. Role of parkin mutations in 111 community-based patients with early-onset parkinsonism [J]. Ann Neurol, 2002, 51: 621-625.
52. Pickrell AM, Youle RJ. The roles of PINK1, parkin, and mitochondrial fidelity in Parkinson's disease [J]. Neuron, 2015, 85:257-273.
53. Koyano F, Matsuda N. Molecular mechanisms underlying PINK1 and Parkin catalyzed ubiquitylation of substrates on damaged mitochondria [J]. Biochim Biophys Acta, 2015, 1853:2791-2796.
54. Vives-Bauza C, Zhou C, Huang Y, et al. P1NK1-dependent recruitment of Parkin to mitochondria in mitophagy [J]. Proc Natl Acad Sci USA, 2010, 107: 378-383.
55. Michiorri S, Gelmetti V, Giarda E, et al. The Parkinson-associated protein PINK1 interacts with Beclinl and promotes autophagy [J]. Cell Death Differ, 2010, 17: 962-974.
56. Gilks WP, Abou-Sleiman PM, Gandhi S, et al. A common LRRK2 mutation in idiopathic Parkinson's disease [J]. Lancet, 2005, 365: 415-416.
57. Verstraeten A, Theuns J, Van Broeckhoven C. Progress in unraveling the genetic etiology of Parkinson disease in a genomic era [J]. Trends Genet, 2015, 31: 140-149.
58. Alegre-Abarrategui J, Christian H, Lufino MM, et al. LRRK2 regulates autophagic activity and localizes to specific membrane microdomains in a novel human genomic reporter cellular model [J]. Hum Mol Genet, 2009, 18:4022-4034.
59. Su YC, Guo X, Qi X. Threonine 56 phosphorylation of Bcl-2 is required for LRRK2 G2019S-induced mitochondrial depolarization and autophagy [J]. Biochim Biophys Acta, 2015, 1852: 12-21.
60. Lachenmayer ML, Yue Z. Genetic animal models for evaluating the role of autophagy in etiopathogenesis of Parkinson disease [J]. Autophagy, 2012, 8: 1837-1838.
61. Daher JP, Volpicelli-Daley LA, Blackburn JP, et al. Abrogation of α-synuclein-mediated dopaminergic neurodegeneration in LRRK2-deficient rats [J]. Proc Natl Acad Sci USA, 2014, 111:9289-9294.
62. Lin X, Parisiadou L, Gu XL, et al. Leucine-rich repeat kinase 2 regulates the progression of neuropathology induced by Parkinson's-disease-related mutant α-synuclein [J]. Neuron, 2009, 64: 807-827.
63. Houlden H, Singleton AB. The genetics and neuropathology of Parkinson's disease [J]. Acta Neuropathol, 2012, 124: 325-338.
64. Cookson MR The role of leucine-rich repeat kinase 2 (LRRK2) in Parkinson's disease [J]. Nat Rev Neurosci, 2010, 11:791-797.
65. Krebiehl G, Ruckerbauer S, Burbulla LF, et al. Reduced basal autophagy and impaired mitochondrial dynamics due to loss of Parkinson's disease-associated protein DJ-1 [J]. PLoS One, 2010, 5: e9367.
66. González-Polo R, Niso-Santano M, Morán JM, et al. Silencing DJ-1 reveals its contribution in paraquat-induced autophagy [J]. J Neurochem, 2009, 109: 889-898.
67. Irrcher I, Aleyasin H, Seifert EL, et al. Loss of the Parkinson's disease-linked gene DJ-1 perturbs mitochondrial dynamics [J]. Hum Mol Genet, 2010, 19: 3734-3746.
68. Thomas KJ, McCoy MK, Blackinton J, et al. DJ-1 acts in parallel to the PINK1/parkin pathway to control mitochondrial function and autophagy [J]. Hum Mol Genet, 2011, 20: 40-50.
69. Vasseur S, Afzal S, Tardivel-Lacombe J, et al. DJ-1/PARK7 is an important mediator of hypoxia-induced cellular responses [J]. Proc Natl Acad Sci USA, 2009, 106:1111-1116.
70. McCoy MK, Cookson MR. DJ-1 regulation of mitochondrial function and autophagy through oxidative stress [J]. Autophagy, 2011, 7: 531-532.
71. Ren H, Fu K, Mu C, et al. DJ-1, a cancer and Parkinson's disease associated protein, regulates autophagy through JNK pathway in cancer cells [J]. Cancer Lett, 2010, 297: 101-108.
72. Pukass K, Richter-Landsberg C. Inhibition of UCH-L1 in oligodendroglial cells results in microtubule stabilization and prevents α-synuclein aggregate formation by activating the autophagic pathway: implications for multiple system atrophy [J]. Front Cell Neurosci, 2015, 9: 163.
73. Ramirez A, Heimbach A, Gründemann J, et al. Hereditary parkinsonism with dementia is caused by mutations in ATP13A2, encoding a lysosomal type 5 P-type ATPase [J]. Nat Genet, 2006, 38:1184-1191.
74. Murphy KE, Gysbers AM, Abbott SK, et al. Reduced gluco-cerebrosidase is associated with increased α-synuclein in sporadic Parkinson's disease [J]. Brain, 2014, 137: 834-848.
75. Valadas JS, Vos M, Verstreken P. Therapeutic strategies in Parkinson's disease: what we have learned from animal models [J]. Ann NY Acad Sci, 2015, 1338: 16-37.
76. Pan T, Kondo S, Zhu W, et al. Neuroprotection of rapamycin in lactacystin-induced neurodegeneration via autophagy enhancement [J]. Neurobiol Dis, 2008, 32: 16-25.
77. Shen W, Henry AG, Paumier KL, et al. Inhibition of gluco-sylceramide synthase stimulates autophagy flux in neurons [J]. J Neurochem, 2014, 129: 884-894.
78. Savolainen MH, Richie CT, Harvey BK, et al. The beneficial effect of a prolyl oligopeptidase inhibitor, KYP-2047, on alpha-synuclein clearance and autophagy in A30P transgenic mouse [J]. Neurobiol Dis, 2014, 68: 1-15.
79. Savolainen MH, Yan X, Myohanen TT, et al. Prolyl oligopeptidase enhances α-synuclein dimerization via direct protein-protein interaction [J]. J Biol Chem, 2015, 290: 5117-5126.
80. Hebron ML, Lonskaya I, Moussa CE. Nilotinib reverses loss of dopamine neurons and improves motor behavior via autophagic degradation of α-synuclein in Parkinson's disease models [J]. Hum Mol Genet, 2013, 22: 3315-3328.
81. Wu Y, Li X, Zhu JX, et al. Resveratrol-activated AMPK/SIRT1/autophagy in cellular models of Parkinson's disease [J]. Neurosignals, 2011, 19: 163-174.
82. Sarkar S, Davies JE, Huang Z, et al. Trehalose, a novel mTOR-independent autophagy enhancer, accelerates the clearance of mutant huntingtin and alpha-synuclein [J]. J Biol Chem, 2007, 282: 5641-5652.
83. Höllerhage M, Goebel JN, de Andrade A, et al. Trifluoperazine rescues human dopaminergic cells from wild-type α-synuclein-induced toxicity [J]. Neurobiol Aging, 2014, 35: 1700-1711.
84. Zhang L, Yu J, Pan H, et al. Small molecule regulators of autophagy identified by an image-based high-throughput screen [J]. Proc Natl Acad Sci USA, 2007, 104: 19023-19028.
85. Steele JW, Ju S, Lachenmayer ML, et al. Latrepirdine stimulates autophagy and reduces accumulation of α-synuclein in cells and in mouse brain [J]. Mol Psychiatry, 2013, 18: 882-888.
86. Xiong N, Jia M, Chen C, et al. Potential autophagy enhancers attenuate rotenone-induced toxicity in SH-SY5Y [J]. Neuroscience, 2011, 199: 292-302.
87. Ryu HW, Oh WK, Jang IS, et al. Amurensin G induces autophagy and attenuates cellular toxicities in a rotenone model of Parkinson's disease [J]. Biochem Biophys Res Commun, 2013, 433: 121-126.
88. Kim HJ, Kim J, Kang KS, et al. Neuroprotective effect of chebulagic acid via autophagy induction in SH-SY5Y cells [J]. Biomol Ther, 2014, 22: 275-281.
89. + and acidic damage via autophagic pathway [J]. J Ethnopharmacol, 2010, 131:122-129.
90. Li XZ, Chen XP, Zhao K, et al. Therapeutic effects of valproate combined with lithium carbonate on MPTP-induced parkinsonism in mice: possible mediation through enhanced autophagy [J]. Int J Neurosci, 2013, 123: 73-79.
91. Su YC, Qi X. Inhibition of excessive mitochondrial fission reduced aberrant autophagy and neuronal damage caused by LRRK2 G2019S mutation [J]. Hum Mol Genet, 2013, 22: 4545-4561.
92. Qi X, Qvit N, Su YC, et al. A novel Drpl inhibitor diminishes aberrant mitochondrial fission and neurotoxicity [J]. J Cell Sci, 2013, 126:789-802.
93. Tovilovic G, Zogovic N, Soskic V, et al. Arylpiperazine-mediated activation of Akt protects SH-SY5Y neuroblastoma cells from 6-hydroxydopamine-induced apoptotic and autophagic death [J]. Neuropharmacology, 2013, 72: 224-235.
94. Zhang S, Gui XH, Huang LP, et al. Neuroprotective effects of β-asarone against 6-hydroxy dopamine-induced parkinsonism via JNK/Bcl-2/Beclin-1 pathway [J]. Mol Neurobiol, 2014. DOI:10.1007/s12035-014-8950-z.