Ubiquitination of α-synuclein is not required for formation of pathological inclusions in α-synucleinopathies

American Journal of Pathology

Volumn 163, Issue 1, 2003, Pages 91-100

  Sampathu, Deepak M ^a   Giasson, Benoit I ^a   Pawlyk, Aaron C ^a   Trojanowski, John Q ^a   Lee, Virginia M Y ^a  

^a UNIVERSITY OF PENNSYLVANIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALPHA SYNUCLEIN; DODECYL SULFATE SODIUM; UBIQUITIN;

ADULT; AGED; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CONTROLLED STUDY; DEGENERATIVE DISEASE; DEMENTIA; FEMALE; GLIA; HUMAN; IMMUNOHISTOCHEMISTRY; LEWY BODY; MALE; MOUSE; NERVE CELL; NONHUMAN; PARKINSON DISEASE; PRIORITY JOURNAL; SHY DRAGER SYNDROME;

EID: 0038307156     PISSN: 00029440     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0002-9440(10)63633-4     Document Type: Article

References (66)

1. Spillantini MG, Goedert M: The α-synucleinopathies: Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy. Ann NY Acad Sci 2000, 920:16-27
2. Duda JE, Lee VM-Y, Trojanowski JQ: Neuropathology of synuclein aggregates. J Neurosci Res 2000, 61:121-127
3. Goedert M: α-Synuclein and neurodegenerative diseases. Nat Rev Neurosci 2001, 2:492-501
4. Polymeropoulos MH, Lavedan C, Leroy E, Ide SE, Dehejia A, Dutra A, Pike B, Root H, Rubenstein Boyer R, Stenroos ES, Chandrasekharappa S, Athanassiadou A, Papapetropoulos T, Johnson WG, Lazzarini AM, Duvoisin RC, Di Iorio G, Golbe LI, Nussbaum RL: Mutation in the α-synuclein gene identified in families with Parkinson's disease. Science 1997, 276:2045-2047
5. Kruger R, Kuhn W, Muller T, Woitalla D, Graeber M, Kosel S, Przuntek H, Epplen JT, Schols L, Riess O: Ala30Pro mutation in the gene encoding α-synuclein in Parkinson's disease. Nat Genet 1998, 18:106-108
6. Spillantini MG, Schmidt ML, Lee VM-Y, Trojanowski JQ, Jakes R, Goedert M: α-Synuclein in Lewy bodies. Nature 1997, 388:839-840
7. Takeda A, Mallory M, Sundsmo M, Honer W, Hansen L, Masliah E: Abnormal accumulation of NACP/α-synuclein in neurodegenerative disorders. Am J Pathol 1998, 152:367-372
8. Wakabayashi K, Matsumoto K, Takayama K, Yoshimoto M, Takahashi H: NACP, a presynaptic protein, immunoreactivity in Lewy bodies in Parkinson's disease. Neurosci Lett 1997, 239:45-48
9. Baba M, Nakajo S, Tu PH, Tomita T, Nakaya K, Lee VM-Y, Trojanowski JQ, Iwatsubo T: Aggregation of α-synuclein in Lewy bodies of sporadic Parkinson's disease and dementia with Lewy bodies. Am J Pathol 1998, 152:879-884
10. Spillantini MG, Crowther RA, Jakes R, Cairns NJ, Lantos PL, Goedert M: Filamentous α-synuclein inclusions link multiple system atrophy with Parkinson's disease and dementia with Lewy bodies. Neurosci Lett 1998, 251:205-208
11. Spillantini MG, Crowther RA, Jakes R, Hasegawa M, Goedert M: α-Synuclein in filamentous inclusions of Lewy bodies from Parkinson's disease and dementia with Lewy bodies. Proc Natl Acad Sci USA 1998, 95:6469-6473
12. Conway KA, Harper JD, Lansbury PT: Accelerated in vitro fibril formation by a mutant α-synuclein linked to early-onset Parkinson disease. Nat Med 1998, 4:1318-1320
13. Giasson BI, Uryu K, Trojanowski JQ, Lee VM-Y: Mutant and wild type human α-synucleins assemble into elongated filaments with distinct morphologies in vitro. J Biol Chem 1999. 274:7619-7622
14. Narhi L, Wood SJ, Steavenson S, Jiang Y, Wu GM, Anafi D, Kaufman SA, Martin F, Sitney K, Denis P, Louis JC, Wypych J, Biere AL. Citron M: Both familial Parkinson's disease mutations accelerate α-synuclein aggregation. J Biol Chem 1999, 274:9843-9846
15. Kahle PJ, Neumann M, Ozmen L, Muller V, Jacobsen H, Schindzielorz A, Okochi M, Leimer U, van der PH, Probst A, Kremmer E, Kretzschmar HA, Haass C: Subcellular localization of wild-type and Parkinson's disease-associated mutant α-synuclein in human and transgenic mouse brain. J Neurosci 2000, 20:6365-6373
16. van der Putten H, Wiederhold KH, Probst A, Barbieri S, Mistl C, Danner S, Kauffmann S, Hofele K, Spooren WP, Ruegg MA, Lin S, Caroni P, Sommer B, Tolnay M, Bilbe G: Neuropathology in mice expressing human α-synuclein. J Neurosci 2000, 20:6021-6029
17. Feany MB, Bender WW: A Drosophila model of Parkinson's disease. Nature 2000, 404:394-398
18. Masliah E, Rockenstein E, Veinbergs I, Mallory M, Hashimoto M, Takeda A, Sagara Y, Sisk A, Mucke L: Dopaminergic loss and inclusion body formation in α-synuclein mice: implications for neurodegenerative disorders. Science 2000, 287:1265-1269
19. Giasson BI, Duda JE, Quinn SM, Zhang B, Trojanowski JQ, Lee VM-Y: Neuronal α-synucleinopathy with severe movement disorder in mice expressing A53T human α-synuclein. Neuron 2002, 34:521-533
20. Auluck PK, Chan HY, Trojanowski JQ, Lee VM-Y, Bonini NM: Chaperone suppression of α-synuclein toxicity in a Drosophila model for Parkinson's disease. Science 2002, 295:865-868
21. Leroy E, Boyer R, Auburger G, Leube B, Ulm G, Mezey E, Harta G, Brownstein MJ, Jonnalagada S, Chernova T, Dehejia A, Lavedan C, Gasser T, Steinbach PJ, Wilkinson KD, Polymeropoulos MH: The ubiquitin pathway in Parkinson's disease. Nature 1998, 395:451-452
22. 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, 392:605-60
23. Giasson BI, Lee VM-Y: Parkin and the molecular pathways of Parkinson's disease. Neuron 2001, 31:885-888
24. Hershko A, Ciechanover A: The ubiquitin system. Annu Rev Biochem 1998, 67:425-479
25. Zhang Y, Gao J, Chung KK, Huang H, Dawson VL, Dawson TM: Parkin functions as an E2-dependent ubiquitin-protein ligase and promotes the degradation of the synaptic vesicle-associated protein, CDCrel-1. Proc Natl Acad Sci USA 2000, 97:13354-13359
26. Imai Y, Soda M, Takahashi R: Parkin suppresses unfolded protein stress-induced cell death through its E3 ubiquitin-protein ligase activity. J Biol Chem 2000, 275:35661-35664
27. Shimura H, Hattori N, Kubo S, Mizuno Y, Asakawa S, Minoshima S, Shimizu N, Iwai K, Chiba T, Tanaka K, Suzuki T: Familial Parkinson disease gene product, parkin, is a ubiquitin-protein ligase. Nat Genet 2000, 25:302-305
28. Chung KK, Zhang Y, Lim KL, Tanaka Y, Huang H, Gao J, Ross CA, Dawson VL, Dawson TM: Parkin ubiquitinates the α-synuclein-interacting protein, synphilin-1: implications for Lewy-body formation in Parkinson disease. Nat Med 2001, 7:1144-1150
29. Imai Y, Soda M, Inoue H, Hattori N, Mizuno Y, Takahashi R: An unfolded putative transmembrane polypeptide, which can lead to endoplasmic reticulum stress, is a substrate of parkin. Cell 2001, 105:891-902
30. Shimura H, Schlossmacher MG, Hattori N, Frosch MP, Trockenbacher A, Schneider R, Mizuno Y, Kosik KS, Selkoe DJ: Ubiquitination of a new form of α-synuclein by parkin from human brain: implications for Parkinson's disease. Science 2001, 293:263-269
31. McNaught KS, Jenner P: Proteasomal function is impaired in substantia nigra in Parkinson's disease. Neurosci Lett 2001, 297:191-194
32. Irizarry MC, Growdon W, Gomez-Isla T, Newell K, George JM, Clayton DF, Hyman BT: Nigral and cortical Lewy bodies and dystrophic nigral neurites in Parkinson's disease and cortical Lewy body disease contain α-synuclein immunoreactivity. J Neuropathol Exp Neurol 1998, 57:334-337
33. Gomez-Tortosa E, Newell K, Irizarry MC, Sanders JL, Hyman BT: α-Synuclein immunoreactivity in dementia with Lewy bodies: morphological staging and comparison with ubiquitin immunostaining. Acta Neuropathol (Berl) 2000, 99:352-357
34. Rideout HJ, Larsen KE, Sulzer D, Stefanis L: Proteasomal inhibition leads to formation of ubiquitin/α-synuclein-immunoreactive inclusions in PC12 cells. J Neurochem 2001, 78:899-908
35. McNaught KS, Mytilineou C, Jnobaptiste R, Yabut J, Shashidharan P, Jennert P, Olanow CW: Impairment of the ubiquitin-proteasome system causes dopaminergic cell death and inclusion body formation in ventral mesencephalic cultures. J Neurochem 2002, 81:301-306
36. Giasson BI, Jakes R, Goedert M, Duda JE, Leight S, Trojanowski JQ, Lee VM-Y: A panel of epitope-specific antibodies detects protein domains distributed throughout human α-synuclein in Lewy bodies of Parkinson's disease. J Neurosci Res 2000, 59:528-533
37. Duda JE, Giasson BI, Mabon ME, Lee VM-Y, Trojanowski JQ: Novel antibodies to synuclein show abundant striatal pathology in Lewy body diseases. Ann Neurol 2002, 52:205-210
38. Haas AL, Bright PM: The immunochemical detection and quantitation of intracellular ubiquitin-protein conjugates. J Biol Chem 1985, 260:12464-12473
39. Schmidt ML, Murray J, Lee VM-Y, Hill WD, Wertkin A, Trojanowski JQ: Epitope map of neurofilament protein domains in cortical and peripheral nervous system Lewy bodies. Am J Pathol 1991, 139:53-65
40. Duda JE, Giasson BI, Gur TL, Montine TJ, Robertson D, Biaggioni I, Hurtig HI, Stern MB, Gollomp SM, Grossman M, Lee VM-Y, Trojanowski JQ: Immunohistochemical and biochemical studies demonstrate a distinct profile of α-synuclein permutations in multiple system atrophy. J Neuropathol Exp Neurol 2000, 59:830-841
41. McKeith IG, Galasko D, Kosaka K, Perry EK, Dickson DW, Hansen LA, Salmon DP, Lowe J, Mirra SS, Byrne EJ, Lennox G, Quinn NP, Edwardson JA, Ince PG, Bergeron C, Burns A, Miller BL, Lovestone S, Collerton D, Jansen EN, Ballard C, De Vos RA, Wilcock GK, Jellinger KA, Perry RH: Consensus guidelines for the clinical and pathologic diagnosis of dementia with Lewy bodies (DLB): report of the consortium on DLB international workshop. Neurology 1996, 47:1113-1124
42. Gilman S, Low PA, Quinn N, Albanese A, Ben Shlomo Y, Fowler CJ, Kaufmann H, Klockgether T, Lang AE, Lantos PL, Litvan I, Mathias CJ, Oliver E, Robertson D, Schatz I, Wenning GK: Consensus statement on the diagnosis of multiple system atrophy. J Neurol Sci 1999, 163:94-98
43. Duda JE, Giasson BI, Chen Q, Gur TL, Hurtig HI, Stern MB, Gollomp SM, Ischiropoulos H, Lee VM-Y, Trojanowski JQ: Widespread nitration of pathological inclusions in neurodegenerative synucleinopathies. Am J Pathol 2000, 157:1439-1445
44. Forman MS, Schmidt ML, Kasturi S, Perl DP, Lee VM-Y, Trojanowski JQ: Tau and α-synuclein pathology in amygdala of parkinsonism-dementia complex patients of Guam. Am J Pathol 2002, 160:1725-1731
45. Giasson BI, Murray IV, Trojanowski JQ, Lee VM-Y: A hydrophobic stretch of 12 amino acid residues in the middle of α-synuclein is essential for filament assembly. J Biol Chem 2001, 276:2380-2386
46. Hershko A, Ciechanover A, Heller H, Haas AL, Rose IA: Proposed role of ATP in protein breakdown: conjugation of protein with multiple chains of the polypeptide of ATP-dependent proteolysis. Proc Natl Acad Sci USA 1980, 77:1783-1786
47. Lowe J, Blanchard A, Morrell K, Lennox G, Reynolds L, Billett M, Landon M, Mayer RJ: Ubiquitin is a common factor in intermediate filament inclusion bodies of diverse type in man, including those of Parkinson's disease, Pick's disease, and Alzheimer's disease, as well as Rosenthal fibres in cerebellar astrocytomas, cytoplasmic bodies in muscle, and Mallory bodies in alcoholic liver disease. J Pathol 1988, 155:9-15
48. Kuzuhara S, Mori H, Izumiyama N, Yoshimura M, Ihara Y: Lewy bodies are ubiquitinated. A light and electron microscopic immunocytochemical study. Acta Neuropathol (Berl) 1988, 75:345-353
49. Papp MI, Kahn JE, Lantos PL: Glial cytoplasmic inclusions in the CNS of patients with multiple system atrophy (striatonigral degeneration, olivopontocerebellar atrophy and Shy-Drager syndrome). J Neurol Sci 1989, 94:79-100
50. Kato S, Nakamura H: Cytoplasmic argyrophilic inclusions in neurons of pontine nuclei in patients with olivopontocerebellar atrophy: immunohistochemical and ultrastructural studies. Acta Neuropathol (Berl) 1990, 79:584-594
51. Kato S, Nakamura H, Hirano A, Ito H, Llena JF, Yen SH: Argyrophilic ubiquitinated cytoplasmic inclusions of Leu-7-positive glial cells in olivopontocerebellar atrophy (multiple system atrophy). Acta Neuropathol (Berl) 1991, 82:488-493
52. Arima K, Murayama S, Mukoyama M, Inose T: Immunocytochemical and ultrastructural studies of neuronal and oligodendroglial cytoplasmic inclusions in multiple system atrophy. 1. Neuronal cytoplasmic inclusions. Acta Neuropathol (Berl) 1992, 83:453-460
53. Murayama S, Arima K, Nakazato Y, Satoh J, Oda M, Inose T: Immunocytochemical and ultrastructural studies of neuronal and oligodendroglial cytoplasmic inclusions in multiple system atrophy 2. Oligodendroglial cytoplasmic inclusions. Acta Neuropathol (Berl) 1992, 84:32-38
54. Hayashi S, Wakabayashi K, Ishikawa A, Nagai H, Saito M, Maruyama M, Takahashi T, Ozawa T, Tsuji S, Takahashi H: An autopsy case of autosomal-recessive juvenile parkinsonism with a homozygous exon 4 deletion in the parkin gene. Mov Disord 2000, 15:884-888
55. Hasegawa M, Fujiwara H, Nonaka T, Wakabayashi K, Takahashi H, Lee VM-Y, Trojanowski JQ, Mann D, Iwatsubo T: Phosphorylated α-synuclein is ubiquitinated in α-synucleinopathy lesions. J Biol Chem 2002, 277:49071-49076
56. Pickart CM, Rose IA: Ubiquitin carboxyl-terminal hydrolase acts on ubiquitin carboxyl-terminal amides. J Biol Chem 1985, 260:7903-7910
57. Wilkinson KD: Ubiquitination and deubiquitination: targeting of proteins for degradation by the proteasome. Semin Cell Dev Biol 2000, 11:141-148
58. Liu Y, Fallon L, Lashuel HA, Liu Z, Lansbury PT Jr: The UCH-L1 gene encodes two opposing enzymatic activities that affect α-synuclein degradation and Parkinson's disease susceptibility. Cell 2002, 111:209-218
59. Jakes R, Spillantini MG, Goedert M: Identification of two distinct synucleins from human brain. FEBS Lett 1994, 345:27-32
60. Leigh PN, Probst A, Dale GE, Power DP, Brion JP, Dodson A, Anderton BH: New aspects of the pathology of neurodegenerative disorders as revealed by ubiquitin antibodies. Acta Neuropathol (Berl) 1989, 79:61-72
61. Dale GE, Probst A, Luthert P, Martin J, Anderton BH, Leigh PN: Relationships between Lewy bodies and pale bodies in Parkinson's disease. Acta Neuropathol (Berl) 1992, 83:525-529
62. Thrower JS, Hoffman L, Rechsteiner M, Pickart CM: Recognition of the polyubiquitin proteolytic signal. EMBO J 2000, 19:94-102
63. Ancolio K, Alves DC, Ueda K, Checler F: α-Synuclein and the Parkinson's disease-related mutant Ala53Thr-α-synuclein do not undergo proteasomal degradation in HEK293 and neuronal cells. Neurosci Lett 2000, 285:79-82
64. Paxinou E, Chen Q, Weisse M, Giasson BI, Norris EH, Rueter SM, Trojanowski JQ, Lee VM-Y, Ischiropoulos H: Induction of α-synuclein aggregation by intracellular nitrative insult. J Neurosci 2001, 21:8053-8061
65. Bennett MC, Bishop JF, Leng Y, Chock PB, Chase TN, Mouradian MM: Degradation of α-synuclein by proteasome. J Biol Chem 1999, 274:33855-33858
66. Tofaris GK, Layfield R, Spillantini MG: α-Synuclein metabolism and aggregation is linked to ubiquitin-independent degradation by the proteasome. FEBS Lett 2001, 509:22-26