Oxidative Damage Linked to Neurodegeneration by Selective α-Synuclein Nitration in Synucleinopathy Lesions
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- 3 November 2000
- journal article
- other
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 290 (5493), 985-989
- https://doi.org/10.1126/science.290.5493.985
Abstract
Aggregated α-synuclein proteins form brain lesions that are hallmarks of neurodegenerative synucleinopathies, and oxidative stress has been implicated in the pathogenesis of some of these disorders. Using antibodies to specific nitrated tyrosine residues in α-synuclein, we demonstrate extensive and widespread accumulations of nitrated α-synuclein in the signature inclusions of Parkinson's disease, dementia with Lewy bodies, the Lewy body variant of Alzheimer's disease, and multiple system atrophy brains. We also show that nitrated α-synuclein is present in the major filamentous building blocks of these inclusions, as well as in the insoluble fractions of affected brain regions of synucleinopathies. The selective and specific nitration of α-synuclein in these disorders provides evidence to directly link oxidative and nitrative damage to the onset and progression of neurodegenerative synucleinopathies.Keywords
This publication has 29 references indexed in Scilit:
- Widespread Nitration of Pathological Inclusions in Neurodegenerative SynucleinopathiesThe American Journal of Pathology, 2000
- Mutant and Wild Type Human α-Synucleins Assemble into Elongated Filaments with Distinct Morphologies in VitroJournal of Biological Chemistry, 1999
- Glial cytoplasmic inclusions in white matter oligodendrocytes of multiple system atrophy brains contain insoluble α‐synucleinAnnals of Neurology, 1998
- Filamentous α-synuclein inclusions link multiple system atrophy with Parkinson's disease and dementia with Lewy bodiesNeuroscience Letters, 1998
- α-Synuclein in filamentous inclusions of Lewy bodies from Parkinson’s disease and dementia with Lewy bodiesProceedings of the National Academy of Sciences, 1998
- AlaSOPro mutation in the gene encoding α-synuclein in Parkinson's diseaseNature Genetics, 1998
- Mutation in the α-Synuclein Gene Identified in Families with Parkinson's DiseaseScience, 1997
- Characterization of a novel protein regulated during the critical period for song learning in the zebra finchNeuron, 1995
- Identification of two distinct synucleins from human brainFEBS Letters, 1994
- Distribution of tau proteins in the normal human central and peripheral nervous system.Journal of Histochemistry & Cytochemistry, 1989