title: Glycogen synthase kinase-3 inhibitors: Rescuers of cognitive impairments.
abstract: Impairment of cognitive processes is a devastating outcome of many diseases, injuries, and drugs affecting the central nervous system (CNS). Most often, very little can be done by available therapeutic interventions to improve cognitive functions. Here we review evidence that inhibition of glycogen synthase kinase-3 (GSK3) ameliorates cognitive deficits in a wide variety of animal models of CNS diseases, including Alzheimer's disease, Fragile X syndrome, Down syndrome, Parkinson's disease, spinocerebellar ataxia type 1, traumatic brain injury, and others. GSK3 inhibitors also improve cognition following impairments caused by therapeutic interventions, such as cranial irradiation for brain tumors. These findings demonstrate that GSK3 inhibitors are able to ameliorate cognitive impairments caused by a diverse array of diseases, injury, and treatments. The improvements in impaired cognition instilled by administration of GSK3 inhibitors appear to involve a variety of different mechanisms, such as supporting long-term potentiation and diminishing long-term depression, promotion of neurogenesis, reduction of inflammation, and increasing a number of neuroprotective mechanisms. The potential for GSK3 inhibitors to repair cognitive deficits associated with many conditions warrants further investigation of their potential for therapeutic interventions, particularly considering the current dearth of treatments available to reduce loss of cognitive functions.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Miller School of Medicine, University of Miami, Miami, FL 33136, USA.
authors.forename: Margaret K
authors.initials: MK
authors.lastname: King
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Miller School of Medicine, University of Miami, Miami, FL 33136, USA.
authors.forename: Marta
authors.initials: M
authors.lastname: Pardo
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Miller School of Medicine, University of Miami, Miami, FL 33136, USA.
authors.forename: Yuyan
authors.initials: Y
authors.lastname: Cheng
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Miller School of Medicine, University of Miami, Miami, FL 33136, USA.
authors.forename: Kimberlee
authors.initials: K
authors.lastname: Downey
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Miller School of Medicine, University of Miami, Miami, FL 33136, USA.
authors.forename: Richard S
authors.initials: RS
authors.lastname: Jope
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Miller School of Medicine, University of Miami, Miami, FL 33136, USA. Electronic address: ebeurel@med.miami.edu.
authors.forename: Eléonore
authors.initials: E
authors.lastname: Beurel
mesh_terms: D000818:Animals; D003072:Cognition Disorders / Q000139:chemically induced / Q000188:drug therapy*; D004195:Disease Models, Animal; D038341:Glycogen Synthase Kinases / Q000037:antagonists & inhibitors*; D006801:Humans; D007249:Inflammation / Q000188:drug therapy; D055495:Neurogenesis / Q000187:drug effects; D009473:Neuronal Plasticity / Q000187:drug effects; D018697:Nootropic Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use*
chemical_list: D018697:Nootropic Agents; D047428:Protein Kinase Inhibitors; D038341:Glycogen Synthase Kinases
keywords: 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; AD; APP; Alzheimer's disease; Aβ; CNS; FX; Fragile X; Fragile X syndrome; GSK3; Glycogen synthase kinase-3; LTD; LTP; Learning; Lithium; MTPT; SCA1; TBI; amyloid precursor protein; amyloid-β peptide; central nervous system; glycogen synthase kinase-3; long-term depression; long-term potentiation; spinocerebellar ataxia type 1; traumatic brain injury
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