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The goal of the present study was to confirm VPA\u2019s dose-dependent neuroprotective propensities in the MPP<jats:sup>+<\/jats:sup>model of PD in primary dopamine (DA) neurons and to investigate the underlying molecular mechanisms using specific mitogen-activated protein kinases (MAPKs) and phosphatidylinositol 3-kinase- (PI3K-) Akt signaling inhibitors. VPA reversed MPP<jats:sup>+<\/jats:sup>-induced mitochondrial apoptosis and counteracted MPP<jats:sup>+<\/jats:sup>-induced extracellular signal-regulated kinase (ERK) and Akt repression and inhibited glycogen synthase kinase 3<jats:italic>\u03b2<\/jats:italic>(GSK3<jats:italic>\u03b2<\/jats:italic>) activation through induction of GSK3<jats:italic>\u03b2<\/jats:italic>phosphorylation. Moreover, inhibitors of the PI3K and MAPK pathways abolished GSK3<jats:italic>\u03b2<\/jats:italic>phosphorylation and diminished the VPA-induced neuroprotective effect. These findings indicated that VPA\u2019s neuroprotective effect in the MPP<jats:sup>+<\/jats:sup>-model of PD is associated with GSK3<jats:italic>\u03b2<\/jats:italic>phosphorylation via Akt and ERK activation in the mitochondrial intrinsic apoptotic pathway. Thus, VPA may be a promising therapeutic candidate for clinical treatment of PD.<\/jats:p>","DOI":"10.1155\/2017\/8124501","type":"journal-article","created":{"date-parts":[[2017,3,22]],"date-time":"2017-03-22T18:12:46Z","timestamp":1490206366000},"page":"1-12","source":"Crossref","is-referenced-by-count":8,"title":["Valproic Acid Protects Primary Dopamine Neurons from MPP<sup>+<\/sup>-Induced Neurotoxicity: Involvement of GSK3<i>\u03b2<\/i>Phosphorylation by Akt and ERK through the Mitochondrial Intrinsic Apoptotic Pathway"],"prefix":"10.1155","volume":"2017","author":[{"given":"Chi","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianrui","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, 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