Widespread nitration of pathological inclusions in neurodegenerative synucleinopathies

Reactive nitrogen species may play a mechanistic rot in neurodegenerative d iseases by posttranslationally altering normal brain proteins. In support o f this hypothesis, we demonstrate that an anti-3-nitrotyrosine polyclonal a ntibody stains all of the major hallmark lesions of synucleinopathies Inclu ding Lewy bodies, Lewy neurites and neuraxonal spheroids in dementia with L ewy bodies, the Lewy body variant of Alzheimer's disease, and neurodegenera tion with brain iron accumulation type 1, as well. as glial and neuronal cy toplasmic inclusions in multiple system atrophy. This antibody predominantl y recognized nitrated alpha -synuclein when compared to other In vitro nitr ated constituents of these pathological lesions, such as neurofilament subu nits and microtubules, Collectively, these findings imply that alpha -synuc lein is nitrated in pathological lesions. The widespread presence of nitrat ed alpha -synuclein in diverse intracellular inclusions suggests that oxida tion/nitration is involved in the onset and/or progression of neurodegenera tive diseases.