Journal
JOURNAL OF NEUROCHEMISTRY
Volume 76, Issue 2, Pages 637-640Publisher
BLACKWELL SCIENCE LTD
DOI: 10.1046/j.1471-4159.2001.00174.x
Keywords
dopaminergic neurons; MPTP; neurodegeneration; Parkinson's disease; substantia nigra; synuclein
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Structural and functional alterations of alpha -synuclein is a presumed culprit in the demise of dopaminergic neurons in Parkinson's disease (PD), alpha -Synuclein mutations are found in familial but not in sporadic PD, raising the hypothesis that effects similar to those of familial PD-linked alpha -synuclein mutations may be achieved by oxidative post-translational modifications. Here, we show that wild-type alpha -synuclein is a selective target for nitration following peroxynitrite exposure of stably transfected HEK293 cells. Nitration of alpha -synuclein also occurs in the mouse striatum and Ventral midbrain following administration of the parkinsonian neurotoxin 1-methyt-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Conversely, beta -synuclein and synaptophysin were not nitrated in MPTP-intoxicated mice. Our data demonstrate that alpha -synuclein is a target for tyrosine nitration, which, by disrupting its biophysical properties, may be relevant to the putative role of alpha -synuclein in the neurodegeneration associated with MPTP toxicity and with PD.
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