title: Association of glycogen synthase kinase-3β with Parkinson's disease (review).
abstract: Glycogen synthase kinase-3 (GSK-3) is a pleiotropic serine/threonine protein kinase found in almost all eukaryotes. It is structurally highly conserved and has been identified as a multifaceted enzyme affecting a wide range of biological functions, including gene expression and cellular processes. There are two closely related isoforms of GSK-3; GSK-3α and GSK-3β. The latter appears to play crucial roles in regulating the pathogenesis of diverse diseases, including neurodegenerative disease. The present review focuses on the involvement of this protein in Parkinson's disease (PD), a common neurodegenerative disorder characterized by the gradually progressive and selective loss of dopaminergic neurons, and by intracellular inclusions known as Lewy bodies (LBs) expressed in surviving neurons of the substantia nigra (SN). GSK-3β is involved in multiple signaling pathways and has several phosphorylation targets. Numerous apoptotic conditions can be facilitated by the GSK-3β signaling pathways. Studies have shown that GSK-3β inhibition protects the dopaminergic neurons from various stress-induced injuries, indicating the involvement of GSK-3β in PD pathogenesis. However, the underlying mechanisms of the protective effect of GSK-3β inhibition on dopaminergic neurons in PD is not completely understood. Multiple pathological events have been recognized to be responsible for the loss of dopaminergic neurons in PD, including mitochondrial dysfunction, oxidative stress, protein aggregation and neuroinflammation. The present review stresses the regulatory roles of GSK-3β in these events and in dopaminergic neuron degeneration, in an attempt to gain an improved understanding of the underlying mechanisms and to provide a potential effective therapeutic target for PD.
authors.affiliation: Department of Neurology, Affiliated Hospital of Beihua University, Jilin, Jilin 132000, P.R. China.
authors.forename: Da-Wei
authors.initials: DW
authors.lastname: Li
authors.affiliation: Department of Neurology, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Zhi-Qiang
authors.initials: ZQ
authors.lastname: Liu
authors.affiliation: Department of Neurology, The Third Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Neurology, The Third Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Min
authors.initials: M
authors.lastname: Yao
authors.affiliation: Department of Neurology, The Third Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Guang-Ren
authors.initials: GR
authors.lastname: Li
mesh_terms: D000818:Animals; D017209:Apoptosis; D042967:Electron Transport Complex I / Q000378:metabolism; D005326:Fetal Proteins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D038362:Glycogen Synthase Kinase 3 / Q000235:genetics / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D010300:Parkinson Disease / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D020825:T-Box Domain Proteins / Q000235:genetics / Q000378:metabolism; D051844:alpha-Synuclein / Q000235:genetics / Q000378:metabolism; D000098908:Brachyury Protein
chemical_list: D042967:Electron Transport Complex I; D005326:Fetal Proteins; D038362:Glycogen Synthase Kinase 3; D000071679:Glycogen Synthase Kinase 3 beta; D017382:Reactive Oxygen Species; D020825:T-Box Domain Proteins; D051844:alpha-Synuclein; D000098908:Brachyury Protein; C000605506:GSK3B protein, human