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Because Parkinson's disease (PD), like sepsis, is associated with iNOS induction, we assessed the existence of changes in iNOS\/i\u2010mtNOS and their relation with mitochondrial dysfunction in the MPTP model of PD, which also displays increased iNOS expression. We also evaluated the role of melatonin (aMT) and its brain metabolite, N<jats:sup>1<\/jats:sup>\u2010acetyl\u20105\u2010methoxykynuramine (AMK), in preventing i\u2010mtNOS induction and mitochondrial failure in this model of PD. Mitochondria from substantia nigra (SN) and, to a lesser extent, from striatum (ST) showed a significant increase in i\u2010mtNOS activity, nitrite levels, oxidative stress, and complex I inhibition after MPTP treatment. MPTP\u2010induced i\u2010mtNOS was probably related to mitochondrial failure, because its prevention by aMT and AMK reduced oxidative\/nitrosative stress and restored complex I activity. These findings represent the first experimental evidence of a potential role for i\u2010mtNOS in the mitochondrial failure of PD and support a novel mechanism in the neuroprotective effects of aMT and AMK. \u00a9 2009 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jnr.22123","type":"journal-article","created":{"date-parts":[[2009,5,12]],"date-time":"2009-05-12T22:11:15Z","timestamp":1242166275000},"page":"3002-3010","source":"Crossref","is-referenced-by-count":94,"title":["Melatonin and its brain metabolite N<sup>1<\/sup>\u2010acetyl\u20105\u2010methoxykynuramine prevent mitochondrial nitric oxide synthase induction in parkinsonian mice"],"prefix":"10.1002","volume":"87","author":[{"given":"V\u00edctor","family":"Tapias","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Germaine","family":"Escames","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis 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