Alpha-Synuclein in Parkinson's Disease: Light from Two New Angles

Annals of Neurology

Volumn 55, Issue 2, 2004, Pages 153-156

  Golbe, Lawrence I ^a   Mouradian, M Maral ^a  

^a ROBERT WOOD JOHNSON MEDICAL SCHOOL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALANINE; ALPHA SYNUCLEIN; BACTERIAL TOXIN; CYTOCHROME C; DOPAMINE; GLUTAMIC ACID; HEAVY METAL; LIPID; LYSINE; METHIONINE; NEUROTRANSMITTER; OLIGOMER; OXIDIZING AGENT; PARKIN; PESTICIDE; PROLINE; PROTEASOME; THREONINE; TYROSINE; UBIQUITIN;

ALPHA HELIX; AMINO ACID SEQUENCE; AMINO ACID SUBSTITUTION; AUTOSOMAL DOMINANT DISORDER; BRAIN NERVE CELL; CELL DEATH; CELL VACUOLE; CELLULAR DISTRIBUTION; DOPAMINE METABOLISM; DOPAMINERGIC NERVE CELL; EDITORIAL; GENE FREQUENCY; GENE IDENTIFICATION; GENE LOCUS; GENE MUTATION; GENE SEQUENCE; GLIA CELL; HAPLOTYPE; HUMAN; LEWY BODY; LINKAGE ANALYSIS; MOLECULAR CLONING; MUTATIONAL ANALYSIS; NERVE DEGENERATION; NONHUMAN; OXIDATIVE STRESS; PARKINSON DISEASE; PATHOPHYSIOLOGY; POINT MUTATION; PRIORITY JOURNAL; PROMOTER REGION; PROTEIN AGGREGATION; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN LIPID INTERACTION; PROTEIN LOCALIZATION; PROTEIN MODIFICATION; PROTEIN POLYMERIZATION; PROTEIN PROCESSING; PROTEIN SECONDARY STRUCTURE; PROTEIN STABILITY; SHY DRAGER SYNDROME;

ALPHA-SYNUCLEIN; HUMANS; MUTATION; NERVE TISSUE PROTEINS; PARKINSON DISEASE; SYNUCLEINS;

EID: 0842282690     PISSN: 03645134     EISSN: None     Source Type: Journal    
DOI: 10.1002/ana.20036     Document Type: Editorial

References (42)

1. Farrer M, Kachergus J, Forno L, et al. Comparison of kindreds with familial parkinsonism and α-synuclein genomic multiplications. Ann Neural 2004;55:174-179.
2. Zarranz J, Alegre J, Gomez-Esteban J, et al. The new mutation, E46K, of a α-synuclein causes Parkinson and lewy body dementia. Ann Neurol 2004;55:164-173.
3. Golbe LI, Di Iorio G, Bonavita V, Miller DC, Duvoisin RC. A large kindred with autosomal dominant Parkinson's disease. Ann Neurol 1990;27:276-282.
4. Polymeropoulos MH, Higgins JJ, Golbe LI, et al. A gene for Parkinson's disease maps to 4q21-q23. Science 1996;274:1197-1199.
5. Polymeropoulos MH, Lavedan C, Leroy E, et al. Mutation in alpha synuclein identified in families with Parkinson's disease. Science 1997;276:2045-2047.
6. Spillantini MG, Schmidt ML, Lee VM, Trojanowski JQ, Jakes R, Goedert M. Alpha-synuclein in Lewy bodies. Nature 1997;388:839-840.
7. Baba M, Nakajo S, Tu PH, et al. Aggregation of alpha-synuclein in Lewy bodies of sporadic Parkinson's disease and dementia with Lewy bodies. Am J Pathol 1998;152:879-884.
8. Markopoulou K, Wszolek ZK, Pfeiffer RF. Reduced expression of the G209A alpha-synuclein allele in familial Parkinsonism. Ann Neurol 1999;46:374-381.
9. Athanassiadou A, Voutsinas G, Psiouri L, et al. Genetic analysis of families with Parkinson disease that carry the Ala53Thr mutation in the gene encoding alpha-synuclein. Am J Hum Genet 1999;65:555-558.
10. Spira PJ, Sharpe DM, Halliday G, Cavanagh J, Nicholson GA. Clinical and pathological features of a Parkinsonian syndrome in a family with an Ala53Thr alpha-synuclein mutation. Ann Neurol 2001;49:313-319.
11. Krüger R, Kuhn W, Müller T, et al. Ala30Pro mutation in the gene encoding alpha-synuclein in Parkinson's disease. Nat Genet 1998;18:106-108.
12. Singleton AB, Farrer M, Johnson J, et al. Alpha-synuclein locus triplication causes Parkinson's disease. Science 2003;302:841.
13. Farrer M, Maraganore DM, Lockhart P, et al. Alpha-synuclein gene haplotypes are associated with Parkinson's disease. Hum Mol Genet 2001;10:1847-1851.
14. Lücking CB, Durr A, Bonifati V, et al. Association between early-onset Parkinson's disease and mutations in the parkin gene. French Parkinson's Disease Genetics Study Group. N Engl J Med 2000;342:1560-1567.
15. Bonifati V, Rizzu P, Squitieri F, et al. DJ-1 (PARK7), a novel gene for autosomal recessive, early onset parkinsonism. Neurol Sci 2003;24:159-160.
16. Willingham S, Fleming Outeiro T, DeVit MJ, Lindquist S, Muchowski PJ. Yeast genes that enhance the toxicity of a mutant huntingtin fragment or α-synuclein. Science 2003;302:1769-1772.
17. Takahashi T, Yamashita H, Nakamura T, Nagano Y, Nakamura S. Tyrosine 125 of α-synuclein plays a critical role for dimerization following nitrative stress. Brain Res 2002;938:73-80.
18. Takahashi M, Kanuka H, Fujiwara H, et al. Phosphorylation of alpha-synuclein characteristic of synucleinopathy lesions is recapitulated in alpha-synuclein transgenic Drosophila. Neurosci Lett 2003;336:155-158.
19. Giasson BI, Duda JE, Murray IV, et al. Oxidative damage linked to neurodegeneration by selective α-synuclein nitration in synucleinopathy lesions. Science 2000;290:985-989.
20. Schwartz DC, Hochstrasser M. A superfamily of protein tags: ubiquitin, SUMO and related modifiers. Trends Biochem Sci. 2003;28:321-328.
21. Chandra S, Chen X, Rizo J, Jahn R, Sudhof TC. A broken alpha-helix in folded alpha-synuclein. J Biol Chem 2003;278:15313-15318.
22. 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.
23. Bence NF, Sampat RM, Kopito RR. Impairment of the ubiquitin-proteasome system by protein aggregation. Science 2001;292:1552-1555.
24. Tanaka Y, Engelender S, Igarashi S, Rao RK, Wanner T, Tanzi RE, et al. Inducible expression of mutant alpha-synuclein decreases proteasome activity and increases sensitivity to mitochondria-dependent apoptosis. Hum Mol Genet 2001;10:919-926.
25. Conway KA, Lee SJ, Rochet JC, Ding TT, Williamson RE, Lansbury PT Jr. Acceleration of oligomerization, not fibrillization, is a shared property of both alpha-synuclein mutations linked to early-onset Parkinson's disease: implications for pathogenesis and therapy. Proc Natl Acad Sci USA 2000;97:571-576.
26. Lashuel HA, Petre BM, Wall J, Simon M, Nowak RJ, Walz T, Lansbuty PT Jr. Alpha-synuclein, especially the Parkinson's disease-associated mutants, forms pore-like annular and tubular protofibrils. J Mol Biol 2002;322:1089-1102.
27. Volles MJ, Lee SJ, Rochet JC, et al. How do α-synuclein aggregates damage dopaminergic neurons? Biochemistry 2001;40:7812-7819.
28. Conway KA, Rochet JC, Bieganski RM, Lansbuty PT Jr. Kinetic stabilization of the alpha-synuclein protofibril by a dopamine-alpha-synuclein adduct. Science 2001;294:1346-1349.
29. Tofaris GK, Layfield R, Spillantini MG. Alpha-synuclein metabolism and aggregation is linked to ubiquitin-independent degradation by the proteasome. FEBS Lett 2001;509:22-26.
30. Masliah E, Rockenstein E, Veinbergs I, et al. Dopaminergic loss and inclusion body formation in alpha-synuclein mice: implications for neurodegenerative disorders. Science 2000;287:1265-1269.
31. Feany MB, Bender WW. A Drosophila model of Parkinson's disease. Nature 2000;404:394-398.
32. Fleming Outeiro T, Lindquist S. Yeast cells provide insight into alpha-synuclein biology and pathobiology. Science 2003;302:1772-1775.
33. Yamin G, Glaser CB, Uversky VN, Fink AL. Certain metals trigger fibrillation of methionine-oxidized alpha-synuclein. J Biol Chem 2003;278:27630-27635.
34. Bennett MC, Bishop JF, Lang Y, Chock PB, Chase TN, Mouradian MM. Degradation of alpha-synuclein by proteasome. J Biol Chem 1999;274:33855-33858.
35. Giasson BI, Forman MS, Higuchi M, et al. Initiation and synergistic fibrillization of tau and alpha-synuclein. Science 2003;300:636-640.
36. Golbe LI, Lazzarini AM, Spychala JR, et al. The tau A0 allele in Parkinson's disease. Movement Disorders 2001;16:442-447.
37. Junn E, Ronchetti RD, Quezado MM, Kim SY, Mouradian MM. Tissue transglutaminase-induced aggregation of alpha-synuclein: Implications for Lewy body formation in Parkinson's disease and dementia with Lewy bodies. Proc Natl Acad Sci USA 2003;100:2047-2052.
38. Kanda S, Bishop JF, Eglitis MA, Yang Y, Mouradian MM. Enhanced vulnerability to oxidative stress by alpha-synuclein mutations and C-terminal truncation. Neuroscience. 2000;97:279-284.
39. Junn E, Mouradian MM. Human alpha-synuclein overexpression increases intracellular reactive oxygen species levels and susceptibility to dopamine. Neurosci Lett 2002 Mar 8;320:146-150.
40. DeStefano AL, Golbe LI, Mark MH, et al. Genome-wide scan for Parkinson's disease: the GenePD Study. Neurology 2001;57:1124-1126.
41. Pankratz N, Nichols WC, Uniacke SK, et al. Genome screen to identify susceptibility genes for Parkinson disease in a sample without parkin mutations. Am J Hum Genet 2002;71:124-135.
42. Scott WK, Nance MA, Watts RL, et al. Complete genomic screen in Parkinson disease: evidence for multiple genes. JAMA 2001;286:2239-2244.