Alpha-synuclein and neurodegenerative diseases (original) (raw)

• Alzheimer, A. Über eine eigenartige Erkrankung der Hirnrinde. Allg. Z. Psychiatr. Psych.-Gerichtl. Med. 64, 146–148 (1907).
  Google Scholar
• Alzheimer, A. Über eigenartige Krankheitsfälle des späteren Alters. Z. ges. Neurol. Psychiatr. 4, 356–385 (1911).
  Article Google Scholar
• Lewy, F. in Handbuch der Neurologie Vol. 3 (eds Lewandowski, M. & Abelsdorff, G.) 920–933 (Springer Verlag, Berlin, 1912).The first description of the inclusions that define Parkinson's disease at a neuropathological level.
  Google Scholar
• Kidd, M. Paired helical filaments in electron microscopy of Alzheimer's disease. Nature 197, 192–193 (1963).
  Article CAS PubMed Google Scholar
• Duffy, P. E. & Tennyson, V. M. Phase and electron microscopic observations of Lewy bodies and melanin granules in the substantia nigra and locus coeruleus in Parkinson's disease. J. Neuropathol. Exp. Neurol. 24, 398–414 (1965).Using electron microscopy, Lewy bodies are shown to contain abnormal filaments.
  Article Google Scholar
• Rewcastle, N. B. & Ball, M. J. Electron microscopic structure of the 'inclusion bodies' in Pick's disease. Neurology 18, 1205–1213 (1968).
  Article CAS PubMed Google Scholar
• Polymeropoulos, M. H. et al. Mutation in the α-synuclein gene identified in families with Parkinson's disease. Science 276, 2045–2047 (1997).A missense mutation in the α-synuclein gene (A53T) causes early-onset familial Parkinson's disease in the Contursi kindred. The first known genetic cause of Parkinson's disease.
  Article CAS PubMed Google Scholar
• Spillantini, M. G. et al. α-synuclein in Lewy bodies. Nature 388, 839–840 (1997).The first description of the presence of α-synuclein in Lewy bodies and Lewy neurites of idiopathic Parkinson's disease and dementia with Lewy bodies.
  Article CAS PubMed Google Scholar
• Lavedan, C. The synuclein family. Genome Res. 2, 871–880 (1998).
  Article Google Scholar
• Clayton, D. F. & George, J. M. Synucleins in synaptic plasticity and neurodegenerative disorders. J. Neurosci. Res. 58, 120–129 (1999).
  Article CAS PubMed Google Scholar
• Maroteaux, L., Campanelli, J. T. & Scheller, R. H. Synuclein: a neuron-specific protein localized to the nucleus and presynaptic terminal. J. Neurosci. 8, 2804–2815 (1988).
  Article CAS PubMed PubMed Central Google Scholar
• Tobe, T. et al. Cloning and characterization of the cDNA encoding a novel brain-specific 14-kDa protein. J. Neurochem. 59, 1624–1629 (1992).
  Article CAS PubMed Google Scholar
• Uéda, K. et al. Molecular cloning of cDNA encoding an unrecognized component of amyloid in Alzheimer disease. Proc. Natl Acad. Sci. USA 90, 11282–11286 (1993).
  Article PubMed PubMed Central Google Scholar
• Bayer, T. A. et al. α-synuclein accumulates in Lewy bodies in Parkinson's disease and dementia with Lewy bodies but not in Alzheimer's disease β-amyloid plaque cores. Neurosci. Lett. 266, 213–216 (1999).
  Article CAS PubMed Google Scholar
• Jakes, R., Spillantini, M. G. & Goedert, M. Identification of two distinct synucleins from human brain. FEBS Lett. 345, 27–32 (1994).
  Article CAS PubMed Google Scholar
• Ji, H. et al. Identification of a breast cancer-specific gene, BCSG1, by direct differential cDNA sequencing. Cancer Res. 57, 759–764 (1997).
  CAS PubMed Google Scholar
• Buchman, V. L. et al. Persyn, a member of the synuclein family, has a distinct pattern of expression in the developing nervous system. J. Neurosci. 18, 9335–9341 (1998).
  Article CAS PubMed PubMed Central Google Scholar
• Davidson, W. S., Jonas, A., Clayton, D. F. & George, J. M. Stabilization of α-synuclein secondary structure upon binding to synthetic membranes. J. Biol. Chem. 273, 9443–9449 (1998).
  Article CAS PubMed Google Scholar
• Jensen, P. H., Nielsen, M. H., Jakes, R., Dotti, C. G. & Goedert, M. Binding of α-synuclein to rat brain vesicles is abolished by familial Parkinson's disease mutation. J. Biol. Chem. 273, 26292–26294 (1998).
  Article CAS PubMed Google Scholar
• McLean, P. J., Kawamata, H., Ribich, S. & Hyman, B. T. Membrane association and protein conformation of α-synuclein in intact neurons. J. Biol. Chem. 275, 8812–8816 (2000).
  Article CAS PubMed Google Scholar
• Jo, E., McLaurin, J. A., Yip, C. M., St George-Hyslop, P. H. & Fraser, P. E. α-synuclein membrane interactions and lipid specificity. J. Biol. Chem. 275, 34328–34334 (2000).
  Article CAS PubMed Google Scholar
• Perrin, R. J., Woods, W. S., Clayton, D. F. & George, J. M. Interaction of human α-synuclein and Parkinson's disease variants with phospholipids. J. Biol. Chem. 275, 34393–34398 (2000).
  Article CAS PubMed Google Scholar
• Eliezer, D., Kutluay, E., Bussell, R. & Browne, G. Conformational properties of α-synuclein in its free and lipid-associated states. J. Mol. Biol. 307, 1061–1073 (2001).
  Article CAS PubMed Google Scholar
• Jenco, J. M., Rawlingson, A., Daniels, B. & Morris, A. J. Regulation of phospholipase D2: selective inhibition of mammalian phospholipase D isoenzymes by _α_- and _β_-synuclein. Biochemistry 37, 4901–4909 (1998).
  Article CAS PubMed Google Scholar
• Okochi, M. et al. Constitutive phosphorylation of the Parkinson's disease-associated α-synuclein. J. Biol. Chem. 275, 390–397 (2000).
  Article CAS PubMed Google Scholar
• Pronin, A. N., Morris, A. J., Surguchov, A. & Benovic, J. L. Synucleins are a novel class of substrates for G protein-coupled receptor kinases. J. Biol. Chem. 275, 26515–26522 (2000).
  Article CAS PubMed Google Scholar
• Engelender, S. et al. Synphilin-1 associates with α-synuclein and promotes the formation of cytosolic inclusions. Nature Genet. 22, 110–114 (1999).
  Article CAS PubMed Google Scholar
• Wakabayashi, K. et al. Synphilin-1 is present in Lewy bodies in Parkinson's disease. Ann. Neurol. 47, 521–523 (2000).
  Article CAS PubMed Google Scholar
• Abeliovich, A. et al. Mice lacking α-synuclein display functional deficits in the nigrostriatal dopamine system. Neuron 25, 239–252 (2000).
  Article CAS PubMed Google Scholar
• Parkinson, J. An Essay on the Shaking Palsy (Sherwood, Neely & Jones, London, 1817).The first clinical description of the disease that became known as Parkinson's disease.
  Google Scholar
• Tretiakoff, C. Contribution à l'étude de l'anatomie pathologique du locus niger de Soemmering avec quelques déductions relatives à la pathogénie des troubles du tonus musculaire et de la maladie de Parkinson. Thesis, Univ. Paris (1919).The first description of pathology in the substantia nigra in Parkinson's disease. Proposal that the inclusions be named after F. Lewy.
  Google Scholar
• Hassler, R. Zur Pathologie der Paralysis agitans und des postenzephalitischen Parkinsonismus. J. Psychol. Neurol. 48, 387–486 (1938).
  Google Scholar
• Forno, L. S. Neuropathology of Parkinson's disease. J. Neuropathol. Exp. Neurol. 55, 259–272 (1996).
  Article CAS PubMed Google Scholar
• Langston, J. W., Ballard, P., Tetrud, J. & Irwin, I. Chronic parkinsonism in humans due to a product of meperidine-analog synthesis. Science 219, 979–980 (1983).
  Article CAS PubMed Google Scholar
• Markey, S. P. et al. Intraneuronal generation of a pyridinium metabolite may cause drug-induced parkinsonism. Nature 311, 464–467 (1984).
  Article CAS PubMed Google Scholar
• Langston, J. W., Irwin, I., Langston, E. B. & Forno, L. S. 1-Methyl-4-phenylpyridinium ion (MPP+): identification of a metabolite of MPTP, a toxin selective to the substantia nigra. Neurosci. Lett. 48, 87–92 (1984).
  Article CAS PubMed Google Scholar
• Javitch, J. A., D'Amato, R. J., Strittmatter, S. M. & Snyder, S. H. Parkinsonism-inducing neurotoxin, _N_-methyl-4-phenyl-1,2,3,6-tetrahydropyridine: uptake of the metabolite _N_-methyl-4-phenylpyridine by dopamine neurons explains selective toxixity. Proc. Natl Acad. Sci. USA 82, 2173–2177 (1985).
  Article CAS PubMed PubMed Central Google Scholar
• Nicklas, W. J., Vyas, I. & Heikkila, R. E. Inhibition of NADP-linked oxidation of brain mitochondria by 1-methyl-4-phenylpyridine, a metabolite of the neurotoxin 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine. Life Sci. 36, 2503–2508 (1985).
  Article CAS PubMed Google Scholar
• Langston, J. W. et al. Evidence of active nerve cell degeneration in the substantia nigra of humans years after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine exposure. Ann. Neurol. 46, 598–605 (1999).
  Article CAS PubMed Google Scholar
• Golbe, L. I. et al. A large kindred with autosomal dominant Parkinson's disease. Ann. Neurol. 27, 276–282 (1990).Description of an early-onset familial form of Parkinson's disease with autopsy-confirmed Lewy body pathology in the Contursi kindred.
  Article CAS PubMed Google Scholar
• Denson, M. A. & Wszolek, Z. K. Familial parkinsonism: our experience and a review of the literature. Parkinsonism Related Disord. 1, 1–8 (1995).
  Article Google Scholar
• Denson, M. A. et al. Familial parkinsonism, dementia, and Lewy body disease: study of family G. Ann. Neurol. 42, 638–643 (1997).
  Article CAS PubMed Google Scholar
• Muenter, M. D. et al. Hereditary form of parkinsonism-dementia. Ann. Neurol. 43, 768–781 (1998).
  Article CAS PubMed Google Scholar
• Mizutani, T. et al. Familial parkinsonism and dementia with ballooned neurons, argyrophilic inclusions, atypical neurofibrillary tangles, tau-negative astrocytic fibrillary tangles, and Lewy bodies. Acta Neuropathol. 95, 15–27 (1998).
  Article CAS PubMed Google Scholar
• Polymeropoulos, M. H. et al. Mapping of a gene for Parkinson's disease to chromosome 4q21-q23. Science 274, 1197–1199 (1996).
  Article CAS PubMed Google Scholar
• Athanassiadou, A. et al. Genetic analysis of families with Parkinson disease that carry the Ala53Thr mutation in the gene encoding α-synuclein. Am. J. Hum. Genet. 65, 555–558 (1999).
  Article CAS PubMed PubMed Central Google Scholar
• Krüger, R. et al. Ala30Pro mutation in the gene encoding α-synuclein in Parkinson's disease. Nature Genet. 18, 106–108 (1998).A second mutation in the α-synuclein gene (A30P) in a family with early-onset Parkinson's disease.
  Article PubMed Google Scholar
• Krüger, R. et al. Increased susceptibility to sporadic Parkinson's disease by a certain combined α-synuclein/apolipoprotein E genotype. Ann. Neurol. 45, 611–617 (1999).
  Article PubMed Google Scholar
• Tan, E. K. et al. Polymorphism of NACP-Rep1 in Parkinson's disease: an etiologic link with essential tremor? Neurology 54, 1195–1198 (2000).
  Article CAS PubMed Google Scholar
• Arima, K. et al. Immunoelectronmicroscopic demonstration of NACP/α-synuclein-epitopes on the filamentous component of Lewy bodies in Parkinson's disease and in dementia with Lewy bodies. Brain Res. 808, 93–100 (1998).
  Article CAS PubMed Google Scholar
• Crowther, R. A., Daniel, S. E. & Goedert, M. Characterisation of isolated α-synuclein filaments from substantia nigra of Parkinson's disease brain. Neurosci. Lett. 292, 128–130 (2000).
  Article CAS PubMed Google Scholar
• Kosaka, K. Lewy bodies in cerebral cortex. Report of three cases. Acta Neuropathol. 42, 127–134 (1978).
  Article CAS PubMed Google Scholar
• Spillantini, M. G., Crowther, R. A., 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 95, 6469–6473 (1998).
  Article CAS PubMed PubMed Central Google Scholar
• Baba, M. et al. Aggregation of α-synuclein in Lewy bodies of sporadic Parkinson's disease and dementia with Lewy bodies. Am. J. Pathol. 152, 879–884 (1998).
  CAS PubMed PubMed Central Google Scholar
• Serpell, L. C., Berriman, J., Jakes, R., Goedert, M. & Crowther, R. A. Fiber diffraction of synthetic α-synuclein filaments shows amyloid-like cross-β conformation. Proc. Natl Acad. Sci. USA 97, 4897–4902 (2000).
  Article CAS PubMed PubMed Central Google Scholar
• Campbell, B. C. et al. Accumulation of insoluble α-synuclein in dementia with Lewy bodies. Neurobiol. Dis. 7, 192–200 (2000).
  Article CAS PubMed Google Scholar
• Iwanaga, K. et al. Lewy body-type degeneration in cardiac plexus in Parkinson's and incidental Lewy body diseases. Neurology 52, 1269–1271 (1999).
  Article CAS PubMed Google Scholar
• Arai, K., Kato, N., Kashiwado, K. & Hattori, T. Pure autonomic failure in association with human α-synucleinopathy. Neurosci. Lett. 296, 171–173 (2000).
  Article CAS PubMed Google Scholar
• Kaufmann, H., Hague, K. & Perl, D. Accumulation of α-synuclein in autonomic nerves in autonomic failure. Neurology 56, 980–981 (2001).
  Article CAS PubMed Google Scholar
• Forno, L. S. Concentric hyaline intraneuronal inclusions of Lewy type in the brain of elderly persons (50 incidental cases): relationship to parkinsonism. J. Am. Geriat. Soc. 17, 557–575 (1969).
  Article CAS PubMed Google Scholar
• Gibb, W. R. G. & Lees, A. J. The relevance of the Lewy body to the pathogenesis of idiopathic Parkinson's disease. J. Neurol. Neurosurg. Psychiat. 51, 745–752 (1988).
  Article CAS PubMed PubMed Central Google Scholar
• Lippa, C. F. et al. Lewy bodies contain altered α-synuclein in brains of many familial Alzheimer's disease patients with mutations in presenilin and amyloid precursor protein genes. Am. J. Pathol. 153, 1365–1370 (1998).
  Article CAS PubMed PubMed Central Google Scholar
• Lippa, C. F., Schmidt, M. L., Lee, V. M.-Y. & Trojanowski, J. Q. Antibodies to α-synuclein detect Lewy bodies in many Down's syndrome brains with Alzheimer's disease. Ann. Neurol. 45, 353–357 (1999).
  Article CAS PubMed Google Scholar
• Tu, P.-H. et al. Glial cytoplasmic inclusions in white matter oligodendrocytes of multiple system atrophy brains contain insoluble α-synuclein. Ann. Neurol. 44, 415–422 (1998).
  Article CAS PubMed Google Scholar
• Yamazaki, M. et al. α-synuclein inclusions in amygdala in the brains of patients with the parkinsonism-dementia complex of Guam. J. Neuropathol. Exp. Neurol. 59, 585–591 (2000).
  Article CAS PubMed Google Scholar
• Spira, P. J. et al. Clinical and pathological features of a parkinsonian syndrome in a family with an Ala53Thr α-synuclein mutation. Ann. Neurol. 49, 313–319 (2001).
  Article CAS PubMed Google Scholar
• Gasser, T. et al. A susceptibility locus for Parkinson's disease maps to chromosome 2p13. Nature Genet. 18, 262–265 (1998).
  Article CAS PubMed Google Scholar
• Farrer, M. et al. A chromosome 4p haplotype segregating with Parkinson's disease and postural tremor. Hum. Mol. Genet. 8, 81–85 (1999).
  Article CAS PubMed Google Scholar
• Gwinn-Hardy, K. et al. Distinctive neuropathology revealed by α-synuclein antibodies in hereditary parkinsonism and dementia linked to chromosome 4p. Acta Neuropathol. 99, 663–672 (2000).
  Article CAS PubMed Google Scholar
• Leroy, E. et al. The ubiquitin pathway in Parkinson's disease. Nature 395, 451–452 (1998).
  Article CAS PubMed Google Scholar
• Kitada, T. et al. Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Nature 392, 605–608 (1998).Identification of mutations in the parkin gene as a genetic cause of autosomal recessive juvenile parkinsonism (AR–JP).
  Article CAS PubMed Google Scholar
• Lücking, C. B. et al. Association between early-onset Parkinson's disease and mutations in the parkin gene. N. Engl. J. Med. 342, 1560–1567 (2000).
  Article PubMed Google Scholar
• Shimura, H. et al. Familial Parkinson disease gene product, parkin, is a ubiquitin-protein ligase. Nature Genet. 25, 302–305 (2000).
  Article CAS PubMed Google Scholar
• Imai, Y., Soda, M. & Takahashi, R. Parkin suppresses unfolded protein stress-induced cell death through its E3 ubiquitin-protein ligase activity. J. Biol. Chem. 275, 35661–35664 (2000).
  Article CAS PubMed Google Scholar
• Zhang, Y. et al. 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 97, 13354–13359 (2000).
  Article CAS PubMed PubMed Central Google Scholar
• Takahashi, H. et al. Familial juvenile parkinsonism: clinical and pathological study in a family. Neurology 44, 437–441 (1994).
  Article CAS PubMed Google Scholar
• Mori, H. et al. Pathologic and biochemical studies of juvenile parkinsonism linked to chromosome 6q. Neurology 51, 890–892 (1998).
  Article CAS PubMed Google Scholar
• Van de Warrenburg, B. P. C. et al. Clinical and pathologic abnormalities in a family with parkinsonism and parkin gene mutations. Neurology 56, 555–557 (2001).
  Article CAS PubMed Google Scholar
• Valente, E. M. et al. Localization of a novel locus for autosomal recessive early-onset parkinsonism, PARK6, on chromosome 1p35-36. Am. J. Hum. Genet. 68, 895–900 (2001).
  Article CAS PubMed PubMed Central Google Scholar
• Wakabayashi, K., Yoshimoto, M., Tsuji, S. & Takahashi, H. α-synuclein immunoreactivity in glial cytoplasmic inclusions in multiple system atrophy. Neurosci. Lett. 249, 180–182 (1998).This and references 64 and 81–83 showed, at about the same time, the presence of α-synuclein in the neuropathological lesions that define multiple system atrophy.
  Article CAS PubMed Google Scholar
• Mezey, E. et al. α-synuclein in neurodegenerative disorders: murderer or accomplice? Nature Med. 4, 755–757 (1998).
  Article CAS PubMed Google Scholar
• Spillantini, M. G. et al. Filamentous α-synuclein inclusions link multiple system atrophy with Parkinson's disease and dementia with Lewy bodies. Neurosci. Lett. 251, 205–208 (1998).
  Article CAS PubMed Google Scholar
• Gai, W. P., Power, J. H., Blumbergs, P. C. & Blessing, W. W. Multiple system atrophy: a new α-synuclein disease? Lancet 352, 547–548 (1998).
  Article CAS PubMed Google Scholar
• Wakabayashi, K. et al. Accumulation of α-synuclein/NACP is a cytopathological feature common to Lewy body disease and multiple system atrophy. Acta Neuropathol. 96, 445–452 (1998).
  Article CAS PubMed Google Scholar
• Papp, M. I., Kahn, J. E. & Lantos, P. L. Glial cytopasmic inclusions in the CNS of patients with multiple system atrophy. J. Neurol. Sci. 94, 79–100 (1989).The first description of the defining neuropathological characteristics of multiple system atrophy.
  Article CAS PubMed Google Scholar
• Lantos, P. L. The definition of multiple system atrophy: a review of recent developments. J. Neuropathol. Exp. Neurol. 57, 1099–1111 (1998).
  Article CAS PubMed Google Scholar
• Wenning, G. K., Quinn, N., Magalhaes, M., Mathias, C. & Daniel, S. E. 'Minimal change' multiple system atrophy. Mov. Disord. 9, 161–166 (1994).
  Article CAS PubMed Google Scholar
• Dickson, D. W. et al. Widespread alterations of α-synuclein in multiple system atrophy. Am. J. Pathol. 155, 1241–1251 (1999).
  Article CAS PubMed PubMed Central Google Scholar
• Campbell, B. C. V. et al. The solubility of α-synuclein in multiple system atrophy differs from that of dementia with Lewy bodies and Parkinson's disease. J. Neurochem. 76, 87–96 (2001).
  Article CAS PubMed Google Scholar
• Weinreb, P. H., Zhen, W., Poon, A. W., Conway, K. A. & Lansbury, P. T. NACP, a protein implicated in Alzheimer's disease and learning, is natively unfolded. Biochemistry 35, 13709–13715 (1996).
  Article CAS PubMed Google Scholar
• Crowther, R. A., Jakes, R., Spillantini, M. G. & Goedert, M. Synthetic filaments assembled from C-terminally truncated α-synuclein. FEBS Lett. 436, 309–312 (1998).
  Article CAS PubMed Google Scholar
• Conway, K. A., Harper, J. D. & Lansbury, P. T. Accelerated in vitro fibril formation by a mutant α-synuclein linked to early-onset Parkinson's disease. Nature Med. 4, 1318–1320 (1998).
  Article CAS PubMed Google Scholar
• El-Agnaf, O. M. A., Jakes, R., Curran, M. D. & Wallace, A. Effects of the mutations Ala30 to Pro and Ala53 to Thr on the physical and morphological properties of α-synuclein protein implicated in Parkinson's disease. FEBS Lett. 440, 67–70 (1998).
  Article CAS PubMed Google Scholar
• Giasson, B. I., Uryu, K., Trojanowski, J. Q. & Lee, V. M.-Y. Mutant and wild-type human α-synuclein assemble into elongated filaments with distinct morphologies in vitro. J. Biol. Chem. 274, 7619–7622 (1999).
  Article CAS PubMed Google Scholar
• Narhi, L. et al. Parkinson's disease mutations accelerate α-synuclein aggregation. J. Biol. Chem. 274, 9843–9846 (1999).
  Article CAS PubMed Google Scholar
• Wood, S. J. et al. α-synuclein fibrillogenesis is nucleation-dependent. J. Biol. Chem. 274, 19509–19512 (1999).
  Article CAS PubMed Google Scholar
• Conway, K. A. et al. Acceleration of oligomerization, not fibrillization, is a shared property of both α-synuclein mutations linked to early-onset Parkinson's disease: implications for pathogenesis and therapy. Proc. Natl Acad. Sci. USA 97, 571–576 (2000).
  Article CAS PubMed PubMed Central Google Scholar
• Conway, K. A., Harper, J. D. & Lansbury, P. T. Fibrils formed in vitro from α-synuclein and two mutant forms linked to Parkinson's disease are typical amyloid. Biochemistry 39, 2552–2563 (2000).
  Article CAS PubMed Google Scholar
• Biere, A. L. et al. Parkinson's disease-associated α-synuclein is more fibrillogenic than β- and γ-synuclein and cannot cross-seed its homologs. J. Biol. Chem. 275, 34574–34579 (2000).
  Article CAS PubMed Google Scholar
• Giasson, B. I., Murray, I. V. J., Trojanowski, J. Q. & Lee, V. M.-Y. A hydrophobic stretch of 12 amino acid residues in the middle of α-synuclein is essential for filament assembly. J. Biol. Chem. 276, 2380–2386 (2001).
  Article CAS PubMed Google Scholar
• Masliah, E. et al. Dopaminergic loss and inclusion body formation in α-synuclein mice: implications for neurodegenerative disorders. Science 287, 1265–1269 (2000).
  Article CAS PubMed Google Scholar
• Van der Putten, H. et al. Neuropathology in mice expressing human α-synuclein. J. Neurosci. 20, 6021–6029 (2000).
  Article PubMed PubMed Central Google Scholar
• Kahle, P. J. et al. Subcellular localization of wild-type and Parkinson's disease-associated mutant α-synuclein in human and transgenic mouse brain. J. Neurosci. 20, 6365–6373 (2000).
  Article CAS PubMed PubMed Central Google Scholar
• Feany, M. B. & Bender, W. W. A Drosophila model of Parkinson's disease. Nature 404, 394–398 (2000).The expression of wild-type and mutant human α-synuclein in nerve cells of Drosophila results in the formation of α-synuclein inclusions, the degeneration of some dopamine nerve cells, and the appearance of locomotor defects.
  Article CAS PubMed Google Scholar
• Perutz, M. F. Glutamine repeats and neurodegenerative diseases: molecular aspects. Trends Biochem. Sci. 24, 58–63 (1999).
  Article CAS PubMed Google Scholar
• Orr, H. T. Beyond the Qs in the polyglutamine diseases. Genes Dev. 15, 925–932 (2001).
  Article CAS PubMed Google Scholar
• Bence, N. F., Sampat, R. M. & Kopito, R. R. Impairment of the ubiquitin-proteasome system by protein aggregation. Science 292, 1552–1555 (2001).
  Article CAS PubMed Google Scholar
• McNaught, K. St. P. & Jenner, P. Proteasomal function is impaired in substantia nigra in Parkinson's disease. Neurosci. Lett. 297, 191–194 (2001).
  Article CAS PubMed Google Scholar
• Betarbet, R. et al. Chronic systemic pesticide exposure reproduces features of Parkinson's disease. Nature Neurosci. 3, 1301–1306 (2000).The chronic administration of rotenone to rats results in the degeneration of dopamine nerve cells in the substantia nigra and the formation of α-synuclein-positive filamentous inclusions that resemble Lewy bodies.
  Article CAS PubMed Google Scholar
• Hensley, K. et al. Interaction of α-phenyl-_N_-_tert_-butyl nitrone and alternative electron acceptors with complex I indicates a substrate reduction site upstream from the rotenone binding site. J. Neurochem. 71, 2549–2557 (1998).
  Article CAS PubMed Google Scholar
• Ostrerova-Golts, N. et al. The A53T α-synuclein mutation increases iron-dependent aggregation and toxicity. J. Neurosci. 20, 6048–6054 (2000).
  Article CAS PubMed PubMed Central Google Scholar
• Uversky, V. N., Li, J. & Fink, A. K. Evidence for a partially folded intermediate in α-synuclein fibril formation. J. Biol. Chem. 276, 10737–10744 (2001).
  Article CAS PubMed Google Scholar
• Hsu, L. J. et al. α-synuclein promotes mitochondrial deficit and oxidative stress. Am. J. Pathol. 157, 401–410 (2000).
  Article CAS PubMed PubMed Central Google Scholar
• Olanow, C. W. & Tatton, W. G. Etiology and pathogenesis of Parkinson's disease. Ann. Rev. Neurosci. 22, 123–144 (1999).
  Article CAS PubMed Google Scholar
• Schapira, A. H. V. Mitochondrial complex I deficiency in Parkinson's disease. Lancet 1, 1269 (1989).
  Article CAS PubMed Google Scholar
• Mizuno, Y. et al. Deficiencies in complex I subunits of the respiratory chain in Parkinson's disease. Biochem. Biophys. Res. Commun. 163, 1450–1455 (1989).
  Article CAS PubMed Google Scholar
• Good, P. F., Hsu, A., Werner, P., Perl, D. P. & Olanow, C. W. Protein nitration in Parkinson's disease. J. Neuropathol. Exp. Neurol. 57, 338–342 (1998).
  Article CAS PubMed Google Scholar
• Giasson, B. I. et al. Oxidative damage linked to neurodegeneration by selective α-synuclein nitration in synucleinopathy lesions. Science 290, 985–989 (2000).
  Article CAS PubMed Google Scholar
• Montagu, K. A. Catechol compounds in rat tissues and in brains of different animals. Nature 180, 244–245 (1957).
  Article CAS PubMed Google Scholar
• Carlsson, A., Lindqvist, M., Magnusson, T. & Waldeck, B. On the presence of 3-hydroxytyramine in brain. Science 127, 471 (1958).
  Article CAS PubMed Google Scholar
• Bertler, A. & Rosengren, E. Occurrence and distribution of dopamine in brain and other tissues. Experientia 15, 10–11 (1959).
  Article CAS PubMed Google Scholar
• Sano, I. et al. Distribution of catechol compounds in human brain. Biochim. Biophys. Acta 32, 586–587 (1959).
  Article CAS PubMed Google Scholar
• Carlsson, A., Lindqvist, M. & Magnusson, T. 3,4-Dihydroxyphenylalanine and 5-hydroxytryptophan as reserpine antagonists. Nature 180, 1200 (1957).
  Article CAS PubMed Google Scholar
• Carlsson, A. The occurrence, distribution and physiological role of catecholamines in the nervous system. Pharmacol. Rev. 11, 490–493 (1959).
  CAS PubMed Google Scholar
• Ehringer, H. & Hornykiewicz, O. Verteilung von Noradrenalin und Dopamin (3-Hydroxytyramin) im Gehirn des Menschen und ihr Verhalten bei Ekrankungen des extrapyramidalen Systems. Klin. Wschr. 38, 1236–1239 (1960).
  Article CAS PubMed Google Scholar
• Marsden, C. D. Parkinson's disease. Lancet 335, 948–952 (1990).
  Article CAS PubMed Google Scholar
• Birkmayer, W. & Hornykiewicz, O. Der L-Dioxyphenylalanin effekt bei der Parkinson-Akinese. Wien. klin. Wschr. 73, 787–788 (1961).
  CAS PubMed Google Scholar
• Barbeau, A., Sourkes, T. L. & Murphy, G. F. in Monoamines et Système Nerveux Central (ed. De Ajuriaguerra, J.) 247–262 (Masson & Cie., Paris, 1962).
  Google Scholar
• Cotzias, G. C., Papavasiliou, P. S. & Fehling, S. Modification of parkinsonism: chronic treatment with L-DOPA. N. Engl. J. Med. 280, 337–345 (1969).
  Article CAS PubMed Google Scholar