The role of glycogen synthase kinase 3 beta in multiple sclerosis.

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 2020 Dec

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Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) that leads to progressive neurological disability due to axonal deterioration. Although MS presents profound heterogeneity in the clinical course, its underlying central mechanism is active demyelination and neurodegeneration associated with inflammation. Multiple autoimmune and neuroinflammatory pathways are involved in the demyelination process of MS. Analysis of MS lesions has shown that inflammatory genes are upregulated. Glycogen synthase kinase-3 (GSK-3) is part of the mitogen-activated protein kinase (MAPK) family and has important roles in many signaling cascades. GSK-3 is a highly conserved serine/threonine protein kinase expressed in both the central and the peripheral nervous systems. GSK-3 modulates several biological processes through phosphorylation of protein kinases, including cell signaling, neuronal growth, apoptosis and production of pro-inflammatory cytokines and interleukins, allowing adaptive changes in events such as cellular proliferation, migration, inflammation, and immunity. GSK-3 occurs in mammals in two isoforms GSK-3α and GSK-3β, both of which are common in the brain, although GSK-3α is found particularly in the cerebral cortex, cerebellum, striated hippocampus and Purkinje cells, while GSK-3β is found in all brain regions. In patients with chronic progressive MS, expression of GSK-3β is elevated in several brain regions such as the corpus callosum and cerebral cortex. GSK-3β inhibition may play a role in glial cell activation, reducing pathological pain induced by nerve injury by formalin injection. According to the role of GSK-3β in pathological conditions, the aim of this article is review of the role of GSK-3β in multiple sclerosis and inflammation of neurons. Copyright © 2020 The Authors. Published by Elsevier Masson SAS.. All rights reserved.

Citation

Tayebeh Noori, Ahmad Reza Dehpour, Antoni Sureda, Sajad Fakhri, Eduardo Sobarzo-Sanchez, Mohammad Hosein Farzaei, Esra Küpeli Akkol, Zahra Khodarahmi, Seyede Zahra Hosseini, Seyede Darya Alavi, Samira Shirooie. The role of glycogen synthase kinase 3 beta in multiple sclerosis. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 2020 Dec;132:110874