Glycogen synthase kinase-3 beta (GSK-3β) signaling

Implications for Parkinson's disease

Mojtaba Golpich, Elham Amini, Fatemeh Hemmati, Norlinah Mohamed Ibrahim, Behrouz Rahmani, Zahurin Mohamed, Raymond Azman Ali, Leila Dargahi, Rasoul Ghasemi, Abolhassan Ahmadiani

Research output: Contribution to journalArticle

90 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)16-26
Number of pages11
JournalPharmacological Research
Volume97
DOIs
Publication statusPublished - 1 Jul 2015

Fingerprint

Parkinson Disease
Neurodegenerative Diseases
Synucleins
Apoptosis
Glycogen Synthase Kinase 3
Glycogen Synthase Kinase 3 beta
alpha-Synuclein
Dopaminergic Neurons
Central Nervous System Diseases
Movement Disorders
Therapeutics
Dopamine
Oxidative Stress
Phosphotransferases

Keywords

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

ASJC Scopus subject areas

  • Pharmacology

Cite this

Glycogen synthase kinase-3 beta (GSK-3β) signaling : Implications for Parkinson's disease. / Golpich, Mojtaba; Amini, Elham; Hemmati, Fatemeh; Mohamed Ibrahim, Norlinah; Rahmani, Behrouz; Mohamed, Zahurin; Ali, Raymond Azman; Dargahi, Leila; Ghasemi, Rasoul; Ahmadiani, Abolhassan.

In: Pharmacological Research, Vol. 97, 01.07.2015, p. 16-26.

Research output: Contribution to journalArticle

Golpich, M, Amini, E, Hemmati, F, Mohamed Ibrahim, N, Rahmani, B, Mohamed, Z, Ali, RA, Dargahi, L, Ghasemi, R & Ahmadiani, A 2015, 'Glycogen synthase kinase-3 beta (GSK-3β) signaling: Implications for Parkinson's disease', Pharmacological Research, vol. 97, pp. 16-26. https://doi.org/10.1016/j.phrs.2015.03.010
Golpich, Mojtaba ; Amini, Elham ; Hemmati, Fatemeh ; Mohamed Ibrahim, Norlinah ; Rahmani, Behrouz ; Mohamed, Zahurin ; Ali, Raymond Azman ; Dargahi, Leila ; Ghasemi, Rasoul ; Ahmadiani, Abolhassan. / Glycogen synthase kinase-3 beta (GSK-3β) signaling : Implications for Parkinson's disease. In: Pharmacological Research. 2015 ; Vol. 97. pp. 16-26.
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