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Drp1, a key regulator of mitochondrial fission, has been shown to be activated and translocated to mitochondria under stress, leading to excessive mitochondria fission and dopaminergic neuronal death <jats:italic>in vitro<\/jats:italic>. However, whether Drp1 inhibition can lead to long term stable preservation of dopaminergic neurons in PD-related mouse models remains unknown. In this study, using a classical MPTP animal PD model, we showed for the first time Drp1 activation and mitochondrial translocation <jats:italic>in vivo<\/jats:italic> after MPTP administration. Inhibition of Drp1 activation by a selective peptide inhibitor P110, blocked MPTP-induced Drp1 mitochondrial translocation and attenuated dopaminergic neuronal loss, dopaminergic nerve terminal damage and behavioral deficits caused by MPTP. MPTP-induced microglial activation and astrogliosis were not affected by P110 treatment. Instead, inhibition of Drp1 mitochondrial translocation diminished MPTP-induced p53, BAX and PUMA mitochondrial translocation. This study demonstrates that inhibition of Drp1 hyperactivation by a Drp1 peptide inhibitor P110 is neuroprotective in a MPTP animal model. Our data also suggest that the protective effects of P110 treatment might be mediated by inhibiting the p53 mediated apoptotic pathways in neurons through inhibition of Drp1-dependent p53 mitochondrial translocation.<\/jats:p>","DOI":"10.1038\/srep32656","type":"journal-article","created":{"date-parts":[[2016,9,13]],"date-time":"2016-09-13T09:11:00Z","timestamp":1473757860000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":152,"title":["Inhibition of Drp1 mitochondrial translocation provides neural protection in dopaminergic system in a Parkinson\u2019s disease model induced by MPTP"],"prefix":"10.1038","volume":"6","author":[{"given":"Emily","family":"Filichia","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barry","family":"Hoffer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Qi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,9,13]]},"reference":[{"key":"BFsrep32656_CR1","doi-asserted-by":"publisher","first-page":"1783","DOI":"10.1016\/S0140-6736(04)16305-8","volume":"363","author":"A Samii","year":"2004","unstructured":"Samii, A., Nutt, J. 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