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It has been proposed that mutated \u03b1\u2010synuclein causes dopaminergic neuron loss by enhancing the vulnerability of these neurons to a variety of insults, including oxidative stress, apoptotic stimuli, and selective dopaminergic neurotoxins, such as 1\u2010methyl\u20104\u2010phenyl\u20101,2,3,6\u2010tetrahydropyridine (MPTP). To test this hypothesis <jats:italic>in vivo<\/jats:italic>, we overexpressed human \u03b1\u2010synuclein<jats:sup>A53T<\/jats:sup> in the substantia nigra of normal and MPTP\u2010treated mice by rAAV\u2010mediated gene transfer. Determination of dopaminergic neuron survival, striatal tyrosine hydroxylase fiber density, and striatal content of dopamine and its metabolites in rAAV\u2010injected and uninjected hemispheres demonstrated that \u03b1\u2010synuclein<jats:sup>A53T<\/jats:sup> does not increase the susceptibility of dopaminergic neurons to MPTP. Our findings argue against a direct detrimental role for (mutant) \u03b1\u2010synuclein in oxidative stress and\/or apoptotic pathways triggered by MPTP, but do not rule out the possibility that \u03b1\u2010synuclein aggregation in neurons exposed to oxidative stress for long periods of time may be neurotoxic. \u00a9 2002 Wiley Periodicals, Inc. J Neurobiol 53: 1\u201310, 2002<\/jats:p>","DOI":"10.1002\/neu.10094","type":"journal-article","created":{"date-parts":[[2002,10,9]],"date-time":"2002-10-09T05:26:15Z","timestamp":1034141175000},"page":"1-10","source":"Crossref","is-referenced-by-count":36,"title":["Overexpression of Parkinson's disease\u2010associated \u03b1\u2010Synuclein<sup>A53T<\/sup> by recombinant adeno\u2010associated virus in mice does not increase the vulnerability of dopaminergic neurons to 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