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(American Journal of Pathology. 2000;157:1439-1445.)
© 2000 American Society for Investigative Pathology

Short Communications

Widespread Nitration of Pathological Inclusions in Neurodegenerative Synucleinopathies

John E. Duda^*, Benoit I. Giasson^*, Qiping Chen, Tamar L. Gur^*, Howard I. Hurtig, Matthew B. Stern, Steven M. Gollomp, Harry Ischiropoulos, Virginia M.-Y. Lee^* and John Q. Trojanowski^*

From the Center for Neurodegenerative Disease Research and Department of Pathology and Laboratory Medicine,^*
and the Department of Neurology,
The University of Pennsylvania, Philadelphia; the Stokes Research Institute and Department of Biochemistry and Biophysics,
Children’s Hospital of Philadelphia and The University of Pennsylvania, Philadelphia, Pennsylvania

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 -synuclein when compared to other in vitro nitrated constituents of these pathological lesions, such as neurofilament subunits and microtubules. Collectively, these findings imply that -synuclein is nitrated in pathological lesions. The widespread presence of nitrated -synuclein in diverse intracellular inclusions suggests that oxidation/nitration is involved in the onset and/or progression of neurodegenerative diseases.

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