Environmental neurotoxic challenge of conditional alpha-synuclein transgenic mice predicts a dopaminergic olfactory-striatal interplay in early PD

Acta Neuropathologica

Volumn 127, Issue 4, 2014, Pages 477-494

  Nuber, Silke ^a   Tadros, Daniel ^a   Fields, Jerel ^b   Overk, Cassia Rose ^a   Ettle, Benjamin ^c   Kosberg, Kori ^a   Mante, Michael ^a   Rockenstein, Edward ^a   Trejo, Margarita ^a   Masliah, Eliezer ^a,b  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

^c UNIVERSITY OF ERLANGEN NUREMBERG   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

ALPHA SYNUCLEIN; CALPAIN; PARAQUAT; UREA;

AMYGDALOID NUCLEUS; ANIMAL EXPERIMENT; ARTICLE; AUTOLYSOSOME; AUTOPHAGY; BRAIN REGION; CELLULAR DISTRIBUTION; COMPLEX FORMATION; CONTROLLED STUDY; CORPUS STRIATUM; CROSS REACTION; DISEASE COURSE; DOPAMINERGIC NERVE CELL; DOPAMINERGIC SYSTEM; HUMAN; HUMAN TISSUE; HYPERACTIVITY; HYPOTHALAMUS; IMMUNOBLOTTING; IMMUNOREACTIVITY; LIMBIC SYSTEM; LOCOMOTION; MESENCEPHALON; MOTIVATION; MOUSE; NERVE DEGENERATION; NEUROTOXICITY; NIGRONEOSTRIATAL SYSTEM; NONHUMAN; OLFACTORY BULB; OLFACTORY SYSTEM; OLIGOMERIZATION; PARKINSON DISEASE; PHENOTYPE; PRIORITY JOURNAL; PROTEIN AGGREGATION; PROTEIN CLEAVAGE; PROTEIN CONFORMATION; PROTEIN EXPRESSION; PROVOCATION TEST; REARING; STEROID RELEASE; STRIATE CORTEX; SYNAPSE; TRANSGENIC MOUSE;

AGED; AGED, 80 AND OVER; ALPHA-SYNUCLEIN; ALZHEIMER DISEASE; ANIMALS; AUTOPHAGY; CELL LINE, TUMOR; CORPUS STRIATUM; DISEASE MODELS, ANIMAL; DOPAMINERGIC NEURONS; FEMALE; GENE EXPRESSION REGULATION; HUMANS; MALE; MICE; MICE, TRANSGENIC; MUTATION; NEURAL PATHWAYS; NEUROTOXINS; OLFACTORY BULB; PARAQUAT;

EID: 84896545055     PISSN: 00016322     EISSN: 14320533     Source Type: Journal    
DOI: 10.1007/s00401-014-1255-5     Document Type: Article

References (108)

1. Anderson JP, Walker DE, Goldstein JM et al (2006) Phosphorylation of is the dominant pathological modification of alpha-synuclein in familial and sporadic Lewy body disease. J Biol Chem 281:29739-29752 (Pubitemid 44536983)
2. Bedard A, Parent A (2004) Evidence of newly generated neurons in the human olfactory bulb. Brain Res Dev Brain Res 151:159-168 (Pubitemid 38887743)
3. Berkowicz DA, Trombley PQ (2000) Dopaminergic modulation at the olfactory nerve synapse. Brain Res 855:90-99 (Pubitemid 30067698)
4. Braak H, Del Tredici K, Rub U et al (2003) Staging of brain pathology related to sporadic Parkinson's disease. Neurobiol Aging 24:197-211 (Pubitemid 36007810)
5. Brodoehl S, Klingner C, Volk GF et al (2012) Decreased olfactory bulb volume in idiopathic Parkinson's disease detected by 3.0-tesla magnetic resonance imaging. Mov Disord 27:1019-1025
6. Brooks AI, Chadwick CA, Gelbard HA et al (1999) Paraquat elicited neurobehavioral syndrome caused by dopaminergic neuron loss. Brain Res 823:1-10 (Pubitemid 29225488)
7. Buchman VL, Ninkina N (2008) Modulation of alpha-synuclein expression in transgenic animals for modelling synucleinopathies-is the juice worth the squeeze? Neurotox Res 14:329-341
8. Cali T, Ottolini D, Brini M (2011) Mitochondria, calcium, and endoplasmic reticulum stress in Parkinson's disease. Biofactors 37:228-240
9. Cali T, Ottolini D, Negro A et al (2012) alpha-Synuclein controls mitochondrial calcium homeostasis by enhancing endoplasmic reticulum- mitochondria interactions. J Biol Chem 287:17914-17929
10. Cappai R, Leck SL, Tew DJ et al (2005) Dopamine promotes alpha-synuclein aggregation into SDS-resistant soluble oligomers via a distinct folding pathway. FASEB J 19:1377-1379 (Pubitemid 41113755)
11. Casadei N, Pohler AM, Tomas-Zapico C et al (2014) Overexpression of synphilin-1 promotes clearance of soluble and misfolded alpha-synuclein without restoring the motor phenotype in aged A30P transgenic mice. Hum Mol Genet 23:767-781
12. Cattarelli M (1982) The role of the medial olfactory pathways in olfaction: behavioral and electrophysiological data. Behav Brain Res 6:339-364
13. Choi BK, Choi MG, Kim JY et al (2013) Large alpha-synuclein oligomers inhibit neuronal SNARE-mediated vesicle docking. Proc Natl Acad Sci USA 110:4087-4092
14. Chu Y, Kordower JH (2007) Age-associated increases of alpha-synuclein in monkeys and humans are associated with nigrostriatal dopamine depletion: is this the target for Parkinson's disease? Neurobiol Dis 25:134-149 (Pubitemid 44765223)
15. Conway KA, Harper JD, Lansbury PT (1998) Accelerated in vitro fibril formation by a mutant alpha-synuclein linked to early-onset Parkinson disease. Nat Med 4:1318-1320 (Pubitemid 28512115)
16. Conway KA, Rochet JC, Bieganski RM et al (2001) Kinetic stabilization of the alpha-synuclein protofibril by a dopamine-alpha-synuclein adduct. Science 294:1346-1349 (Pubitemid 33063102)
17. Cookson MR, van der Brug M (2008) Cell systems and the toxic mechanism(s) of alpha-synuclein. Exp Neurol 209:5-11
18. Crews L, Spencer B, Desplats P et al (2010) Selective molecular alterations in the autophagy pathway in patients with Lewy body disease and in models of alpha-synucleinopathy. PLoS One 5:e9313
19. Cuervo AM, Dice JF (2000) Regulation of lamp2a levels in the lysosomal membrane. Traffic 1:570-583
20. Daher JP, Ying M, Banerjee R et al (2009) Conditional transgenic mice expressing C-terminally truncated human alpha-synuclein (alphaSyn119) exhibit reduced striatal dopamine without loss of nigrostriatal pathway dopaminergic neurons. Mol Neurodegener 4:34
21. Dauer W, Kholodilov N, Vila M et al (2002) Resistance of alpha -synuclein null mice to the parkinsonian neurotoxin MPTP. Proc Natl Acad Sci USA 99:14524-14529 (Pubitemid 35257704)
22. De Tullio R, Cantoni C, Broggio C et al (2009) Involvement of exon 6-mediated calpastatin intracellular movements in the modulation of calpain activation. Biochim Biophys Acta 1790:182-187
23. Di Monte D, Sandy MS, Ekstrom G et al (1986) Comparative studies on the mechanisms of paraquat and 1-methyl-4-phenylpyridine (MPP+) cytotoxicity. Biochem Biophys Res Commun 137:303-309 (Pubitemid 16056066)
24. Doty RL (2008) The olfactory vector hypothesis of neurodegenerative disease: is it viable? Ann Neurol 63:7-15
25. Doty RL (2012) Olfaction in Parkinson's disease and related disorders. Neurobiol Dis 46:527-552
26. Dufty BM, Warner LR, Hou ST et al (2007) Calpain-cleavage of alpha-synuclein: connecting proteolytic processing to disease-linked aggregation. Am J Pathol 170:1725-1738 (Pubitemid 47339316)
27. Feng LR, Maguire-Zeiss KA (2011) Dopamine and paraquat enhance alpha-synuclein-induced alterations in membrane conductance. Neurotox Res 20:387-401
28. Fernagut PO, Hutson CB, Fleming SM et al (2007) Behavioral and histopathological consequences of paraquat intoxication in mice: effects of alpha-synuclein over-expression. Synapse 61:991-1001 (Pubitemid 350271779)
29. Fleming SM, Salcedo J, Fernagut PO et al (2004) Early and progressive sensorimotor anomalies in mice overexpressing wild-type human alpha-synuclein. J Neurosci 24:9434-9440 (Pubitemid 39426179)
30. Freichel C, Neumann M, Ballard T et al (2007) Age-dependent cognitive decline and amygdala pathology in alpha-synuclein transgenic mice. Neurobiol Aging 28:1421-1435 (Pubitemid 47081234)
31. Games D, Seubert P, Rockenstein E et al (2013) Axonopathy in an alpha-synuclein transgenic model of Lewy body disease is associated with extensive accumulation of C-terminal-truncated alpha-synuclein. Am J Pathol 182:940-953
32. Gasser T (2009) Molecular pathogenesis of Parkinson disease: insights from genetic studies. Expert Rev Mol Med 11:e22
33. Gomez-Isla T, Irizarry MC, Mariash A et al (2003) Motor dysfunction and gliosis with preserved dopaminergic markers in human alpha-synuclein A30P transgenic mice. Neurobiol Aging 24:245-258 (Pubitemid 36005405)
34. Graham DR, Sidhu A (2010) Mice expressing the A53T mutant form of human alpha-synuclein exhibit hyperactivity and reduced anxiety-like behavior. J Neurosci Res 88:1777-1783
35. Hawkes CH, Shephard BC, Daniel SE (1997) Olfactory dysfunction in Parkinson's disease. J Neurol Neurosurg Psychiatry 62:436-446 (Pubitemid 27237050)
36. Huisman E, Uylings HB, Hoogland PV (2008) Gender-related changes in increase of dopaminergic neurons in the olfactory bulb of Parkinson's disease patients. Mov Disord 23:1407-1413
37. Kabeya Y, Mizushima N, Ueno T et al (2000) LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing. EMBO J 19:5720-5728
38. Katzenschlager R, Lees AJ (2004) Olfaction and Parkinson's syndromes: its role in differential diagnosis. Curr Opin Neurol 17:417-423 (Pubitemid 39071417)
39. Kertelge L, Bruggemann N, Schmidt A et al (2010) Impaired sense of smell and color discrimination in monogenic and idiopathic Parkinson's disease. Mov Disord 25:2665-2669
40. Kirik D, Rosenblad C, Burger C et al (2002) Parkinson-like neurodegeneration induced by targeted overexpression of alpha-synuclein in the nigrostriatal system. J Neurosci 22:2780-2791 (Pubitemid 37465827)
41. Koprich JB, Johnston TH, Huot P et al (2011) Progressive neurodegeneration or endogenous compensation in an animal model of Parkinson's disease produced by decreasing doses of alpha-synuclein. PLoS One 6:e17698
42. Kordower JH, Bjorklund A (2013) Trophic factor gene therapy for Parkinson's disease. Mov Disord 28:96-109
43. Kurz A, Double KL, Lastres-Becker I et al (2010) A53T-alpha-synuclein overexpression impairs dopamine signaling and striatal synaptic plasticity in old mice. PLoS One 5:e11464
44. Lam HA, Wu N, Cely I et al (2011) Elevated tonic extracellular dopamine concentration and altered dopamine modulation of synaptic activity precede dopamine loss in the striatum of mice overexpressing human alpha-synuclein. J Neurosci Res 89:1091-1102
45. Lelan F, Boyer C, Thinard R et al (2011) Effects of human alpha-synuclein A53T-A30P mutations on SVZ and local olfactory bulb cell proliferation in a transgenic rat model of Parkinson disease. Parkinsons Dis 2011:987084
46. Li W, West N, Colla E et al (2005) Aggregation promoting C-terminal truncation of alpha-synuclein is a normal cellular process and is enhanced by the familial Parkinson's disease-linked mutations. Proc Natl Acad Sci USA 102:2162-2167 (Pubitemid 40262029)
47. Lindvall O (2013) Developing dopaminergic cell therapy for Parkinson's disease - give up or move forward? Mov Disord 28:268-273
48. Liu CW, Giasson BI, Lewis KA et al (2005) A precipitating role for truncated alpha-synuclein and the proteasome in alpha-synuclein aggregation: implications for pathogenesis of Parkinson disease. J Biol Chem 280:22670-22678 (Pubitemid 40853171)
49. Lo Bianco C, Schneider BL, Bauer M et al (2004) Lentiviral vector delivery of parkin prevents dopaminergic degeneration in an alpha-synuclein rat model of Parkinson's disease. Proc Natl Acad Sci USA 101:17510-17515 (Pubitemid 39657434)
50. Lonskaya I, Hebron ML, Algarzae NK et al (2012) Decreased parkin solubility is associated with impairment of autophagy in the nigrostriatum of sporadic Parkinson's disease. Neuroscience 232C:90
51. Mai S, Muster B, Bereiter-Hahn J et al (2012) Autophagy proteins LC3B, ATG5 and ATG12 participate in quality control after mitochondrial damage and influence lifespan. Autophagy 8:47-62
52. Makino S, Smith MA, Gold PW (2002) Regulatory role of glucocorticoids and glucocorticoid receptor mRNA levels on tyrosine hydroxylase gene expression in the locus coeruleus during repeated immobilization stress. Brain Res 943:216-223 (Pubitemid 36120381)
53. Manning-Bog AB, McCormack AL, Li J et al (2002) The herbicide paraquat causes up-regulation and aggregation of alpha-synuclein in mice: paraquat and alpha-synuclein. J Biol Chem 277:1641-1644 (Pubitemid 34968732)
54. Markey KA, Towle AC, Sze PY (1982) Glucocorticoid influence on tyrosine hydroxylase activity in mouse locus coeruleus during postnatal development. Endocrinology 111:1519-1523
55. Markopoulou K, Larsen KW, Wszolek EK et al (1997) Olfactory dysfunction in familial Parkinsonism. Neurology 49:1262-1267 (Pubitemid 27495626)
56. Marxreiter F, Nuber S, Kandasamy M et al (2009) Changes in adult olfactory bulb neurogenesis in mice expressing the A30P mutant form of alpha-synuclein. Eur J Neurosci 29:879-890
57. Masini CV, Holmes PV, Freeman KG et al (2004) Dopamine overflow is increased in olfactory bulbectomized rats: an in vivo microdialysis study. Physiol Behav 81:111-119 (Pubitemid 38430047)
58. Masliah E, Rockenstein E, Veinbergs I et al (2000) Dopaminergic loss and inclusion body formation in alpha-synuclein mice: implications for neurodegenerative disorders. Science 287:1265-1269 (Pubitemid 30112148)
59. May VE, Nuber S, Marxreiter F et al (2012) Impaired olfactory bulb neurogenesis depends on the presence of human wild-type alpha-synuclein. Neuroscience 222:343-355
60. McArthur S, McHale E, Gillies GE (2007) The size and distribution of midbrain dopaminergic populations are permanently altered by perinatal glucocorticoid exposure in a sex- region- and time-specific manner. Neuropsychopharmacology 32:1462-1476 (Pubitemid 46920154)
61. Melachroinou K, Xilouri M, Emmanouilidou E et al (2013) Deregulation of calcium homeostasis mediates secreted alpha-synuclein-induced neurotoxicity. Neurobiol Aging 34:2853-2865
62. Mishizen-Eberz AJ, Norris EH, Giasson BI et al (2005) Cleavage of alpha-synuclein by calpain: potential role in degradation of fibrillized and nitrated species of alpha-synuclein. Biochemistry 44:7818-7829 (Pubitemid 40740765)
63. Mosharov EV, Larsen KE, Kanter E et al (2009) Interplay between cytosolic dopamine, calcium, and alpha-synuclein causes selective death of substantia nigra neurons. Neuron 62:218-229
64. Mouatt-Prigent A, Karlsson JO, Agid Y et al (1996) Increased M-calpain expression in the mesencephalon of patients with Parkinson's disease but not in other neurodegenerative disorders involving the mesencephalon: a role in nerve cell death? Neuroscience 73:979-987 (Pubitemid 26194324)
65. Muller T, Fuchs G, Hahne M et al (2006) Diagnostic aspects of early Parkinson's disease. J Neurol 253(Suppl 4):IV29-IV31
66. Mundinano IC, Caballero MC, Ordonez C et al (2011) Increased dopaminergic cells and protein aggregates in the olfactory bulb of patients with neurodegenerative disorders. Acta Neuropathol 122:61-74
67. Muntane G, Ferrer I, Martinez-Vicente M (2012) alpha-Synuclein phosphorylation and truncation are normal events in the adult human brain. Neuroscience 200:106-119
68. Nemani VM, Lu W, Berge V et al (2010) Increased expression of alpha-synuclein reduces neurotransmitter release by inhibiting synaptic vesicle reclustering after endocytosis. Neuron 65:66-79
69. Norris EH, Uryu K, Leight S et al (2007) Pesticide exposure exacerbates alpha-synucleinopathy in an A53T transgenic mouse model. Am J Pathol 170:658-666 (Pubitemid 47339402)
70. Nuber S, Harmuth F, Kohl Z et al (2013) A progressive dopaminergic phenotype associated with neurotoxic conversion of alpha-synuclein in BAC-transgenic rats. Brain 136:412-432
71. Nuber S, Petrasch-Parwez E, Arias-Carrion O et al (2011) Olfactory neuron-specific expression of A30P alpha-synuclein exacerbates dopamine deficiency and hyperactivity in a novel conditional model of early Parkinson's disease stages. Neurobiol Dis 44:192-204
72. Ortiz J, Fitzgerald LW, Lane S et al (1996) Biochemical adaptations in the mesolimbic dopamine system in response to repeated stress. Neuropsychopharmacology 14:443-452 (Pubitemid 26271175)
73. Outeiro TF, Klucken J, Bercury K et al (2009) Dopamine-induced conformational changes in alpha-synuclein. PLoS One 4:e6906
74. Pearce RK, Hawkes CH, Daniel SE (1995) The anterior olfactory nucleus in Parkinson's disease. Mov Disord 10:283-287
75. Perez RG, Waymire JC, Lin E et al (2002) A role for alpha-synuclein in the regulation of dopamine biosynthesis. J Neurosci 22:3090-3099 (Pubitemid 35379198)
76. Perrin RJ, Payton JE, Barnett DH et al (2003) Epitope mapping and specificity of the anti-alpha-synuclein monoclonal antibody Syn-1 in mouse brain and cultured cell lines. Neurosci Lett 349:133-135 (Pubitemid 37297831)
77. Pinching AJ, Powell TP (1971) The neuron types of the glomerular layer of the olfactory bulb. J Cell Sci 9:305-345
78. Prediger RD, Aguiar AS Jr, Matheus FC et al (2012) Intranasal administration of neurotoxicants in animals: support for the olfactory vector hypothesis of Parkinson's disease. Neurotox Res 21:90-116
79. Recchia A, Rota D, Debetto P et al (2008) Generation of a alpha-synuclein-based rat model of Parkinson's disease. Neurobiol Dis 30:8-18
80. Ricaurte GA, Guillery RW, Seiden LS et al (1982) Dopamine nerve terminal degeneration produced by high doses of methyl-amphetamine in the rat brain. Brain Res 235:93-103 (Pubitemid 12188130)
81. Rothman SM, Griffioen KJ, Vranis N et al (2013) Neuronal expression of familial Parkinson's disease A53T alpha-synuclein causes early motor impairment, reduced anxiety and potential sleep disturbances in mice. J Parkinsons Dis 3:215-229
82. Seidel K, Schols L, Nuber S et al (2010) First appraisal of brain pathology owing to A30P mutant alpha-synuclein. Ann Neurol 67:684-689
83. Sekine T, Kagaya H, Funayama M et al (2010) Clinical course of the first Asian family with Parkinsonism related to SNCA triplication. Mov Disord 25:2871-2875
84. Sengoku R, Saito Y, Ikemura M et al (2008) Incidence and extent of Lewy body-related alpha-synucleinopathy in aging human olfactory bulb. J Neuropathol Exp Neurol 67:1072-1083
85. Singleton AB, Farrer M, Johnson J et al (2003) alpha-Synuclein locus triplication causes Parkinson's disease. Science 302:841 (Pubitemid 37339619)
86. Stifanese R, Averna M, De Tullio R et al (2010) Adaptive modifications in the calpain/calpastatin system in brain cells after persistent alteration in Ca2+ homeostasis. J Biol Chem 285:631-643
87. Tamamizu-Kato S, Kosaraju MG, Kato H et al (2006) Calcium-triggered membrane interaction of the alpha-synuclein acidic tail. Biochemistry 45:10947-10956 (Pubitemid 44360164)
88. Tiscornia G, Singer O, Verma IM (2006) Production and purification of lentiviral vectors. Nat Protoc 1:241-245
89. Tofaris GK, Razzaq A, Ghetti B et al (2003) Ubiquitination of alpha-synuclein in Lewy bodies is a pathological event not associated with impairment of proteasome function. J Biol Chem 278:44405-44411 (Pubitemid 37377190)
90. Ubhi K, Rockenstein E, Mante M et al (2010) Neurodegeneration in a transgenic mouse model of multiple system atrophy is associated with altered expression of oligodendroglial-derived neurotrophic factors. J Neurosci 30:6236-6246
91. Ulusoy A, Febbraro F, Jensen PH et al (2010) Co-expression of C-terminal truncated alpha-synuclein enhances full-length alpha-synuclein-induced pathology. Eur J Neurosci 32:409-422
92. Unger EL, Eve DJ, Perez XA et al (2006) Locomotor hyperactivity and alterations in dopamine neurotransmission are associated with overexpression of A53T mutant human alpha-synuclein in mice. Neurobiol Dis 21:431-443 (Pubitemid 43099866)
93. Uversky VN, Li J, Fink AL (2001) Pesticides directly accelerate the rate of alpha-synuclein fibril formation: a possible factor in Parkinson's disease. FEBS Lett 500:105-108 (Pubitemid 32607541)
94. Volles MJ, Lee SJ, Rochet JC et al (2001) Vesicle permeabilization by protofibrillar alpha-synuclein: implications for the pathogenesis and treatment of Parkinson's disease. Biochemistry 40:7812-7819 (Pubitemid 32622972)
95. Volpicelli-Daley LA, Luk KC, Patel TP et al (2011) Exogenous alpha-synuclein fibrils induce Lewy body pathology leading to synaptic dysfunction and neuron death. Neuron 72:57-71
96. Vosler PS, Brennan CS, Chen J (2008) Calpain-mediated signaling mechanisms in neuronal injury and neurodegeneration. Mol Neurobiol 38:78-100
97. Watanabe Y, Tatebe H, Taguchi K et al (2012) p62/SQSTM1-dependent autophagy of Lewy body-like alpha-synuclein inclusions. PLoS One 7:e52868
98. Welberg LA, Seckl JR, Holmes MC (2001) Prenatal glucocorticoid programming of brain corticosteroid receptors and cortico-trophin- releasing hormone: possible implications for behaviour. Neuroscience 104:71-79 (Pubitemid 32322614)
99. Wersinger C, Sidhu A (2005) Disruption of the interaction of alpha-synuclein with microtubules enhances cell surface recruitment of the dopamine transporter. Biochemistry 44:13612-13624 (Pubitemid 41443689)
100. West MJ, Slomianka L, Gundersen HJ (1991) Unbiased stereological estimation of the total number of neurons in the subdivisions of the rat hippocampus using the optical fractionator. Anat Rec 231:482-497
101. Wills J, Credle J, Oaks AW et al (2012) Paraquat, but not maneb, induces synucleinopathy and tauopathy in striata of mice through inhibition of proteasomal and autophagic pathways. PLoS One 7:e30745
102. Wilson DA, Sullivan RM (1995) The D2 antagonist spiperone mimics the effects of olfactory deprivation on mitral/tufted cell odor response patterns. J Neurosci 15:5574-5581
103. Wilson DA, Wood JG (1992) Functional consequences of unilateral olfactory deprivation: time-course and age sensitivity. Neuroscience 49:183-192
104. Winner B, Geyer M, Couillard-Despres S et al (2006) Striatal deafferentation increases dopaminergic neurogenesis in the adult olfactory bulb. Exp Neurol 197:113-121 (Pubitemid 41817225)
105. Xia HG, Zhang L, Chen G et al (2010) Control of basal autophagy by calpain1 mediated cleavage of ATG5. Autophagy 6:61-66
106. Yamakado H, Moriwaki Y, Yamasaki N et al (2012) alpha-Synuclein BAC transgenic mice as a model for Parkinson's disease manifested decreased anxiety-like behavior and hyperlocomotion. Neurosci Res 73:173-177
107. Yang W, Tiffany-Castiglioni E (2008) Paraquat-induced apoptosis in human neuroblastoma SH-SY5Y cells: involvement of p53 and mitochondria. J Toxicol Environ Health A 71:289-299 (Pubitemid 351218582)
108. Yu S, Zuo X, Li Y et al (2004) Inhibition of tyrosine hydroxylase expression in alpha-synuclein-transfected dopaminergic neuronal cells. Neurosci Lett 367:34-39 (Pubitemid 39078779)