Glycogen Synthase Kinase-3 Beta (GSK-3β) Signaling: Implications for Parkinson's Disease

Pharmacological Research, 2015, DOI:10.1016/j.phrs.2015.03.010

29 Pages Posted: 5 Apr 2015

See all articles by Mojtaba Golpich

Mojtaba Golpich

Department of Medicine, Universiti Kebangsaan Malaysia Medical Centre, Cheras, Kuala Lumpur, Malaysia

Elham Amini

National University of Malaysia (UKM) - Medical Centre

Fatemeh Hemmati

University of Malaya (UM) - Faculty of Medicine

Norlinah Mohamed Ibrahim

National University of Malaysia (UKM)

Behrouz Rahmani

Neuroscience Research Center

Zahurin Mohamed

University of Malaya (UM) - Department of Pharmacology, Faculty of Medicine

Azman Ali Raymond

National University of Malaysia (UKM)

Leila Dargahi

Shahid Beheshti University

Rasoul Ghasemi

Shahid Beheshti University of Medical Sciences

Abolhassan Ahmadiani

Neuroscience Research Center

Date Written: March 28, 2015

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.

Keywords: Parkinson's disease; Glycogen synthase kinase 3; Neuroinflammation; Alpha-Synuclein; Tauopathy; ER stress; Mitochondrial dysfunction

Suggested Citation

Golpich, Mojtaba and Amini, Elham and Hemmati, Fatemeh and Mohamed Ibrahim, Norlinah and Rahmani, Behrouz and Mohamed, Zahurin and Raymond, Azman Ali and Dargahi, Leila and Ghasemi, Rasoul and Ahmadiani, Abolhassan, Glycogen Synthase Kinase-3 Beta (GSK-3β) Signaling: Implications for Parkinson's Disease (March 28, 2015). Pharmacological Research, 2015, DOI:10.1016/j.phrs.2015.03.010. Available at SSRN: https://ssrn.com/abstract=2589609

Mojtaba Golpich (Contact Author)

Department of Medicine, Universiti Kebangsaan Malaysia Medical Centre, Cheras, Kuala Lumpur, Malaysia ( email )

Kuala Lumpur
Malaysia

HOME PAGE: http://www.ppukm.ukm.my/wbppukm/

Elham Amini

National University of Malaysia (UKM) - Medical Centre ( email )

Kuala Lumpur
Malaysia

HOME PAGE: http://www.ppukm.ukm.my/wbppukm/

Fatemeh Hemmati

University of Malaya (UM) - Faculty of Medicine ( email )

Kuala Lumpur, 50603
Malaysia

Norlinah Mohamed Ibrahim

National University of Malaysia (UKM) ( email )

Institute of Climate Change (IPI)
Selengor
Malaysia

Behrouz Rahmani

Neuroscience Research Center ( email )

Daneshjoo BLVD, Evin Square
Tehran, 1983963113
Iran

Zahurin Mohamed

University of Malaya (UM) - Department of Pharmacology, Faculty of Medicine ( email )

Kuala Lumpur, 50603
Malaysia

Azman Ali Raymond

National University of Malaysia (UKM) ( email )

Institute of Climate Change (IPI)
Selengor
Malaysia

Leila Dargahi

Shahid Beheshti University ( email )

Velenjak
Bostan
Tehran, Tehran 19839
Iran

Rasoul Ghasemi

Shahid Beheshti University of Medical Sciences ( email )

Velenjak Street, Shahid Chamran High Way
Tehran
Iran

Abolhassan Ahmadiani

Neuroscience Research Center ( email )

Velenjak Street, Shahid Chamran High Way
Tehran
Iran

Register to save articles to
your library

Register

Paper statistics

Downloads
6
Abstract Views
241
PlumX Metrics