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Oxidative Damage Linked to Neurodegeneration by Selective α-Synuclein Nitration in Synucleinopathy Lesions

Science  03 Nov 2000:
Vol. 290, Issue 5493, pp. 985-989
DOI: 10.1126/science.290.5493.985

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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.

  • * These authors contributed equally to this work.

  • To whom correspondence should be addressed. E-mail: vmylee{at}mail.med.upenn.edu

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