Oxidative damage linked to neurodegeneration by selective alpha-synuclein nitration in synucleinopathy lesions

Aggregated alpha -synuclein proteins form brain Lesions that are hallmarks of neurodegenerative synucleinopathies, and oxidative stress has been impli cated in the pathogenesis of some of these disorders. Using antibodies to s pecific nitrated tyrosine residues in alpha -synuclein, we demonstrate exte nsive and widespread accumulations of nitrated alpha -synuclein in the sign ature inclusions of Parkinson's disease, dementia with Lewy bodies, the Lew y body variant of Alzheimer's disease, and multiple system atrophy brains. We also show that nitrated alpha -synuclein is present in the major filamen tous building blocks of these inclusions, as well as in the insoluble fract ions of affected brain regions of synucleinopathies. The selective and spec ific nitration of alpha -synuclein in these disorders provides evidence to directly link oxidative and nitrative damage to the onset and progression o f neurodegenerative synucleinopathies.