title: Glycogen synthase kinase-3 beta (GSK-3β) signaling: Implications for Parkinson's disease.
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.affiliation: Department of Medicine, Universiti Kebangsaan Malaysia Medical Centre, Cheras, Kuala Lumpur, Malaysia.
authors.forename: Mojtaba
authors.initials: M
authors.lastname: Golpich
authors.affiliation: Department of Medicine, Universiti Kebangsaan Malaysia Medical Centre, Cheras, Kuala Lumpur, Malaysia.
authors.forename: Elham
authors.initials: E
authors.lastname: Amini
authors.affiliation: Department of Medicine, Universiti Kebangsaan Malaysia Medical Centre, Cheras, Kuala Lumpur, Malaysia.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Hemmati
authors.affiliation: Department of Medicine, Universiti Kebangsaan Malaysia Medical Centre, Cheras, Kuala Lumpur, Malaysia.
authors.forename: Norlinah Mohamed
authors.initials: NM
authors.lastname: Ibrahim
authors.affiliation: Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Behrouz
authors.initials: B
authors.lastname: Rahmani
authors.affiliation: Department of Pharmacology, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia.
authors.forename: Zahurin
authors.initials: Z
authors.lastname: Mohamed
authors.affiliation: Department of Medicine, Universiti Kebangsaan Malaysia Medical Centre, Cheras, Kuala Lumpur, Malaysia.
authors.forename: Azman Ali
authors.initials: AA
authors.lastname: Raymond
authors.affiliation: NeuroBiology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Leila
authors.initials: L
authors.lastname: Dargahi
authors.affiliation: Neurophysiology Research Center and Department of Physiology, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address: Rghasemi60@sbmu.ac.ir.
authors.forename: Rasoul
authors.initials: R
authors.lastname: Ghasemi
authors.affiliation: 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.
authors.forename: Abolhassan
authors.initials: A
authors.lastname: Ahmadiani
mesh_terms: D000978:Antiparkinson Agents / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000502:physiology*; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D007249:Inflammation / Q000503:physiopathology; D010300:Parkinson Disease / Q000188:drug therapy* / Q000201:enzymology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
chemical_list: D000978:Antiparkinson Agents; D004791:Enzyme Inhibitors; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3
keywords: Alpha-Synuclein; ER stress; Glycogen synthase kinase 3; Mitochondrial dysfunction; Neuroinflammation; Parkinson's disease; Tauopathy