Widespread nitration of pathological inclusions in neurodegenerative synucleinopathies

JE Duda, BI Giasson, Q Chen, TL Gur, HI Hurtig… - The American journal of …, 2000 - Elsevier
JE Duda, BI Giasson, Q Chen, TL Gur, HI Hurtig, MB Stern, SM Gollomp, H Ischiropoulos
The American journal of pathology, 2000Elsevier
Reactive nitrogen species may play a mechanistic role in neurodegenerative diseases by
posttranslationally altering normal brain proteins. In support of this hypothesis, we
demonstrate that an anti-3-nitrotyrosine polyclonal antibody stains all of the major hallmark
lesions of synucleinopathies including Lewy bodies, Lewy neurites and neuraxonal
spheroids in dementia with Lewy bodies, the Lewy body variant of Alzheimer's disease, and
neurodegeneration with brain iron accumulation type 1, as well as glial and neuronal …
Reactive nitrogen species may play a mechanistic role in neurodegenerative diseases by posttranslationally altering normal brain proteins. In support of this hypothesis, we demonstrate that an anti-3-nitrotyrosine polyclonal antibody stains all of the major hallmark lesions of synucleinopathies including Lewy bodies, Lewy neurites and neuraxonal spheroids in dementia with Lewy bodies, the Lewy body variant of Alzheimer's disease, and neurodegeneration with brain iron accumulation type 1, as well as glial and neuronal cytoplasmic inclusions in multiple system atrophy. This antibody predominantly recognized nitrated α-synuclein when compared to other in vitro nitrated constituents of these pathological lesions, such as neurofilament subunits and microtubules. Collectively, these findings imply that α-synuclein is nitrated in pathological lesions. The widespread presence of nitrated α-synuclein in diverse intracellular inclusions suggests that oxidation/nitration is involved in the onset and/or progression of neurodegenerative diseases.
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