The role of glycogen synthase kinase 3 beta in multiple sclerosis


Noori T., Dehpour A. R. , Sureda A., Fakhri S., Sobarzo-Sanchez E., Farzaei M. H. , ...More

BIOMEDICINE & PHARMACOTHERAPY, vol.132, 2020 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Review
  • Volume: 132
  • Publication Date: 2020
  • Doi Number: 10.1016/j.biopha.2020.110874
  • Journal Name: BIOMEDICINE & PHARMACOTHERAPY
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, CAB Abstracts, EMBASE, Food Science & Technology Abstracts, MEDLINE, Veterinary Science Database
  • Keywords: Multiple sclerosis, Glycogen synthase kinase-3, Inflammation, GSK-3, Neurodegenerative disease, NF-KAPPA-B, EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS, SIGNALING PATHWAY, PROTEIN-KINASE, OLIGODENDROCYTE DIFFERENTIATION, OXIDATIVE STRESS, AXONAL INTEGRITY, GSK-3 INHIBITORS, CATENIN PATHWAY, DENDRITIC CELLS
  • Gazi University Affiliated: Yes

Abstract

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 pro-cess of MS. Analysis of MS lesions has shown that inflammatory genes are upregulated. Glycogen synthase kinase3 (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 pro-tein 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-3 alpha and GSK-313, both of which are common in the brain, although GSK-3 alpha is found particularly in the cerebral cortex, cerebellum, striated hippocampus and Purkinje cells, while GSK-313 is found in all brain regions. In patients with chronic progressive MS, expression of GSK-313 is elevated in several brain regions such as the corpus callosum and cerebral cortex. GSK-313 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-313 in pathological conditions, the aim of this article is review of the role of GSK-313 in multiple sclerosis and inflammation of neurons.