title: Pivotal role of glycogen synthase kinase-3: A therapeutic target for Alzheimer's disease.
abstract: Neurodegenerative diseases are among the most challenging diseases with poorly known mechanism of cause and paucity of complete cure. Out of all the neurodegenerative diseases, Alzheimer's disease is the most devastating and loosening of thinking and judging ability disease that occurs in the old age people. Many hypotheses came forth in order to explain its causes. In this review, we have enlightened Glycogen Synthase Kinase-3 which has been considered as a concrete cause for Alzheimer's disease. Plaques and Tangles (abnormal structures) are the basic suspects in damaging and killing of nerve cells wherein Glycogen Synthase Kinase-3 has a key role in the formation of these fatal accumulations. Various Glycogen Synthase Kinase-3 inhibitors have been reported to reduce the amount of amyloid-beta as well as the tau hyperphosphorylation in both neuronal and nonneuronal cells. Additionally, Glycogen Synthase Kinase-3 inhibitors have been reported to enhance the adult hippocampal neurogenesis in vivo as well as in vitro. Keeping the chemotype of the reported Glycogen Synthase Kinase-3 inhibitors in consideration, they may be grouped into natural inhibitors, inorganic metal ions, organo-synthetic, and peptide like inhibitors. On the basis of their mode of binding to the constituent enzyme, they may also be grouped as ATP, nonATP, and allosteric binding sites competitive inhibitors. ATP competitive inhibitors were known earlier inhibitors but they lack efficient selectivity. This led to find the new ways for the enzyme inhibition.
authors.affiliation: Department of Chemistry, Jamia Millia Islamia, Central University, New Delhi 110025, India.
authors.forename: Mudasir
authors.initials: M
authors.lastname: Maqbool
authors.affiliation: Department of Chemistry, Jamia Millia Islamia, Central University, New Delhi 110025, India; SciLifeLab, Department of Medical Biochemistry and Biophysics (MBB), Karolinska Institute, Box 1031, 17121 Stockholm, Sweden.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Mobashir
authors.affiliation: Department of Chemistry, Jamia Millia Islamia, Central University, New Delhi 110025, India. Electronic address: nhoda@jmi.ac.in.
authors.forename: Nasimul
authors.initials: N
authors.lastname: Hoda
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000473:pathology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D003920:Diabetes Mellitus / Q000188:drug therapy / Q000201:enzymology; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors / Q000502:physiology*; D006624:Hippocampus / Q000187:drug effects; D006801:Humans; D007004:Hypoglycemic Agents / Q000737:chemistry / Q000494:pharmacology; D007249:Inflammation / Q000188:drug therapy / Q000201:enzymology; D058990:Molecular Targeted Therapy / Q000379:methods*; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000970:Antineoplastic Agents; D007004:Hypoglycemic Agents; D047428:Protein Kinase Inhibitors; D038362:Glycogen Synthase Kinase 3
keywords: Alzheimer's disease (AD); Amyloid-beta; Glycogen synthase Kinase-3 (GSK-3); Neurodegenerative diseases (ND); Plaques; Tangles