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Valproic Acid Protects Primary Dopamine Neurons from MPP+-Induced Neurotoxicity: Involvement of GSK3β Phosphorylation by Akt and ERK through the Mitochondrial Intrinsic Apoptotic Pathway
Joint Authors
Zhang, Chi
Yuan, Xianrui
Hu, Zhongliang
Liu, Songlin
Li, Haoyu
Wu, Ming
Yuan, Jian
Zhao, Zijin
Su, Jun
Wang, Xiangyu
Liao, Yiwei
Liu, Qing
Source
Issue
Vol. 2017, Issue 2017 (31 Dec. 2017), pp.1-12, 12 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2017-03-22
Country of Publication
Egypt
No. of Pages
12
Main Subjects
Abstract EN
Valproic acid (VPA), a drug widely used to treat manic disorder and epilepsy, has recently shown neuroprotective effects in several neurological diseases, particularly in Parkinson’s disease (PD).
The goal of the present study was to confirm VPA’s dose-dependent neuroprotective propensities in the MPP+ 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+-induced mitochondrial apoptosis and counteracted MPP+-induced extracellular signal-regulated kinase (ERK) and Akt repression and inhibited glycogen synthase kinase 3β (GSK3β) activation through induction of GSK3β phosphorylation.
Moreover, inhibitors of the PI3K and MAPK pathways abolished GSK3β phosphorylation and diminished the VPA-induced neuroprotective effect.
These findings indicated that VPA’s neuroprotective effect in the MPP+-model of PD is associated with GSK3β 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.
American Psychological Association (APA)
Zhang, Chi& Yuan, Xianrui& Hu, Zhongliang& Liu, Songlin& Li, Haoyu& Wu, Ming…[et al.]. 2017. Valproic Acid Protects Primary Dopamine Neurons from MPP+-Induced Neurotoxicity: Involvement of GSK3β Phosphorylation by Akt and ERK through the Mitochondrial Intrinsic Apoptotic Pathway. BioMed Research International،Vol. 2017, no. 2017, pp.1-12.
https://search.emarefa.net/detail/BIM-1138916
Modern Language Association (MLA)
Zhang, Chi…[et al.]. Valproic Acid Protects Primary Dopamine Neurons from MPP+-Induced Neurotoxicity: Involvement of GSK3β Phosphorylation by Akt and ERK through the Mitochondrial Intrinsic Apoptotic Pathway. BioMed Research International No. 2017 (2017), pp.1-12.
https://search.emarefa.net/detail/BIM-1138916
American Medical Association (AMA)
Zhang, Chi& Yuan, Xianrui& Hu, Zhongliang& Liu, Songlin& Li, Haoyu& Wu, Ming…[et al.]. Valproic Acid Protects Primary Dopamine Neurons from MPP+-Induced Neurotoxicity: Involvement of GSK3β Phosphorylation by Akt and ERK through the Mitochondrial Intrinsic Apoptotic Pathway. BioMed Research International. 2017. Vol. 2017, no. 2017, pp.1-12.
https://search.emarefa.net/detail/BIM-1138916
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1138916