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Glycogen synthase kinase-3 beta (GSK-3β) signaling: Implications for Parkinson's disease.
Pharmacol Res. 2015 Jul; 97:16-26.PR

Abstract

Glycogen synthase kinase 3 (GSK-3) dysregulation plays an important role in the pathogenesis of numerous disorders, affecting the central nervous system (CNS) encompassing both neuroinflammation and neurodegenerative diseases. Several lines of evidence have illustrated a key role of the GSK-3 and its cellular and molecular signaling cascades in the control of neuroinflammation. Glycogen synthase kinase 3 beta (GSK-3β), one of the GSK-3 isomers, plays a major role in neuronal apoptosis and its inhibition decreases expression of alpha-Synuclein (α-Synuclein), which make this kinase an attractive therapeutic target for neurodegenerative disorders. Parkinson's disease (PD) is a chronic neurodegenerative movement disorder characterized by the progressive and massive loss of dopaminergic neurons by neuronal apoptosis in the substantia nigra pars compacta and depletion of dopamine in the striatum, which lead to pathological and clinical abnormalities. Thus, understanding the role of GSK-3β in PD will enhance our knowledge of the basic mechanisms underlying the pathogenesis of this disorder and facilitate the identification of new therapeutic avenues. In recent years, GSK-3β has been shown to play essential roles in modulating a variety of cellular functions, which have prompted efforts to develop GSK-3β inhibitors as therapeutics. In this review, we summarize GSK-3 signaling pathways and its association with neuroinflammation. Moreover, we highlight the interaction between GSK-3β and several cellular processes involved in the pathogenesis of PD, including the accumulation of α-Synuclein aggregates, oxidative stress and mitochondrial dysfunction. Finally, we discuss about GSK-3β inhibitors as a potential therapeutic strategy in PD.

Authors+Show Affiliations

Department of Medicine, Universiti Kebangsaan Malaysia Medical Centre, Cheras, Kuala Lumpur, Malaysia.Department of Medicine, Universiti Kebangsaan Malaysia Medical Centre, Cheras, Kuala Lumpur, Malaysia.Department of Medicine, Universiti Kebangsaan Malaysia Medical Centre, Cheras, Kuala Lumpur, Malaysia.Department of Medicine, Universiti Kebangsaan Malaysia Medical Centre, Cheras, Kuala Lumpur, Malaysia.Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.Department of Pharmacology, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia.Department of Medicine, Universiti Kebangsaan Malaysia Medical Centre, Cheras, Kuala Lumpur, Malaysia.NeuroBiology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.Neurophysiology Research Center and Department of Physiology, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address: Rghasemi60@sbmu.ac.ir.Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Department of Pharmacology, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia. Electronic address: aahmadiani@yahoo.com.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

25829335

Citation

Golpich, Mojtaba, et al. "Glycogen Synthase Kinase-3 Beta (GSK-3β) Signaling: Implications for Parkinson's Disease." Pharmacological Research, vol. 97, 2015, pp. 16-26.
Golpich M, Amini E, Hemmati F, et al. Glycogen synthase kinase-3 beta (GSK-3β) signaling: Implications for Parkinson's disease. Pharmacol Res. 2015;97:16-26.
Golpich, M., Amini, E., Hemmati, F., Ibrahim, N. M., Rahmani, B., Mohamed, Z., Raymond, A. A., Dargahi, L., Ghasemi, R., & Ahmadiani, A. (2015). Glycogen synthase kinase-3 beta (GSK-3β) signaling: Implications for Parkinson's disease. Pharmacological Research, 97, 16-26. https://doi.org/10.1016/j.phrs.2015.03.010
Golpich M, et al. Glycogen Synthase Kinase-3 Beta (GSK-3β) Signaling: Implications for Parkinson's Disease. Pharmacol Res. 2015;97:16-26. PubMed PMID: 25829335.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Glycogen synthase kinase-3 beta (GSK-3β) signaling: Implications for Parkinson's disease. AU - Golpich,Mojtaba, AU - Amini,Elham, AU - Hemmati,Fatemeh, AU - Ibrahim,Norlinah Mohamed, AU - Rahmani,Behrouz, AU - Mohamed,Zahurin, AU - Raymond,Azman Ali, AU - Dargahi,Leila, AU - Ghasemi,Rasoul, AU - Ahmadiani,Abolhassan, Y1 - 2015/03/28/ PY - 2014/12/16/received PY - 2015/03/05/revised PY - 2015/03/16/accepted PY - 2015/4/2/entrez PY - 2015/4/2/pubmed PY - 2016/3/2/medline KW - Alpha-Synuclein KW - ER stress KW - Glycogen synthase kinase 3 KW - Mitochondrial dysfunction KW - Neuroinflammation KW - Parkinson's disease KW - Tauopathy SP - 16 EP - 26 JF - Pharmacological research JO - Pharmacol Res VL - 97 N2 - Glycogen synthase kinase 3 (GSK-3) dysregulation plays an important role in the pathogenesis of numerous disorders, affecting the central nervous system (CNS) encompassing both neuroinflammation and neurodegenerative diseases. Several lines of evidence have illustrated a key role of the GSK-3 and its cellular and molecular signaling cascades in the control of neuroinflammation. Glycogen synthase kinase 3 beta (GSK-3β), one of the GSK-3 isomers, plays a major role in neuronal apoptosis and its inhibition decreases expression of alpha-Synuclein (α-Synuclein), which make this kinase an attractive therapeutic target for neurodegenerative disorders. Parkinson's disease (PD) is a chronic neurodegenerative movement disorder characterized by the progressive and massive loss of dopaminergic neurons by neuronal apoptosis in the substantia nigra pars compacta and depletion of dopamine in the striatum, which lead to pathological and clinical abnormalities. Thus, understanding the role of GSK-3β in PD will enhance our knowledge of the basic mechanisms underlying the pathogenesis of this disorder and facilitate the identification of new therapeutic avenues. In recent years, GSK-3β has been shown to play essential roles in modulating a variety of cellular functions, which have prompted efforts to develop GSK-3β inhibitors as therapeutics. In this review, we summarize GSK-3 signaling pathways and its association with neuroinflammation. Moreover, we highlight the interaction between GSK-3β and several cellular processes involved in the pathogenesis of PD, including the accumulation of α-Synuclein aggregates, oxidative stress and mitochondrial dysfunction. Finally, we discuss about GSK-3β inhibitors as a potential therapeutic strategy in PD. SN - 1096-1186 UR - https://www.unboundmedicine.com/medline/citation/25829335/Glycogen_synthase_kinase_3_beta__GSK_3β__signaling:_Implications_for_Parkinson's_disease_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1043-6618(15)00049-3 DB - PRIME DP - Unbound Medicine ER -