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Association of glycogen synthase kinase-3β with Parkinson's disease (review).
Mol Med Rep. 2014 Jun; 9(6):2043-50.MM

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+Show Affiliations

Department of Neurology, Affiliated Hospital of Beihua University, Jilin, Jilin 132000, P.R. China.Department of Neurology, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.Department of Neurology, The Third Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.Department of Neurology, The Third Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.Department of Neurology, The Third Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

24681994

Citation

Li, Da-Wei, et al. "Association of Glycogen Synthase Kinase-3β With Parkinson's Disease (review)." Molecular Medicine Reports, vol. 9, no. 6, 2014, pp. 2043-50.
Li DW, Liu ZQ, Chen W, et al. Association of glycogen synthase kinase-3β with Parkinson's disease (review). Mol Med Rep. 2014;9(6):2043-50.
Li, D. W., Liu, Z. Q., Chen, W., Yao, M., & Li, G. R. (2014). Association of glycogen synthase kinase-3β with Parkinson's disease (review). Molecular Medicine Reports, 9(6), 2043-50. https://doi.org/10.3892/mmr.2014.2080
Li DW, et al. Association of Glycogen Synthase Kinase-3β With Parkinson's Disease (review). Mol Med Rep. 2014;9(6):2043-50. PubMed PMID: 24681994.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Association of glycogen synthase kinase-3β with Parkinson's disease (review). AU - Li,Da-Wei, AU - Liu,Zhi-Qiang, AU - Chen,Wei, AU - Yao,Min, AU - Li,Guang-Ren, Y1 - 2014/03/28/ PY - 2013/07/22/received PY - 2014/02/25/accepted PY - 2014/4/1/entrez PY - 2014/4/1/pubmed PY - 2015/1/6/medline SP - 2043 EP - 50 JF - Molecular medicine reports JO - Mol Med Rep VL - 9 IS - 6 N2 - 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. SN - 1791-3004 UR - https://www.unboundmedicine.com/medline/citation/24681994/Association_of_glycogen_synthase_kinase_3β_with_Parkinson's_disease__review__ DB - PRIME DP - Unbound Medicine ER -