Glycogen synthase kinase-3 inhibitors

Rescuers of cognitive impairments

Margaret K. King, Marta Pardo, Yuyan Cheng, Kimberlee Downey, Richard S Jope, Eleonore Beurel

Research output: Contribution to journalArticle

86 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1-12
Number of pages12
JournalPharmacology and Therapeutics
Volume141
Issue number1
DOIs
StatePublished - Jan 1 2014

Fingerprint

Glycogen Synthase Kinase 3
Cognition
Central Nervous System Agents
Cranial Irradiation
Spinocerebellar Ataxias
Therapeutics
Fragile X Syndrome
Long-Term Potentiation
Central Nervous System Diseases
Neurogenesis
Wounds and Injuries
Down Syndrome
Brain Neoplasms
Parkinson Disease
Alzheimer Disease
Animal Models
Cognitive Dysfunction
Depression
Inflammation

Keywords

  • Alzheimer's disease
  • Fragile X syndrome
  • Glycogen synthase kinase-3
  • Learning
  • Lithium
  • LTP

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

Cite this

Glycogen synthase kinase-3 inhibitors : Rescuers of cognitive impairments. / King, Margaret K.; Pardo, Marta; Cheng, Yuyan; Downey, Kimberlee; Jope, Richard S; Beurel, Eleonore.

In: Pharmacology and Therapeutics, Vol. 141, No. 1, 01.01.2014, p. 1-12.

Research output: Contribution to journalArticle

King, Margaret K. ; Pardo, Marta ; Cheng, Yuyan ; Downey, Kimberlee ; Jope, Richard S ; Beurel, Eleonore. / Glycogen synthase kinase-3 inhibitors : Rescuers of cognitive impairments. In: Pharmacology and Therapeutics. 2014 ; Vol. 141, No. 1. pp. 1-12.
@article{4e70c5f3dba7412ca734b86258aec2fc,
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.",
keywords = "Alzheimer's disease, Fragile X syndrome, Glycogen synthase kinase-3, Learning, Lithium, LTP",
author = "King, {Margaret K.} and Marta Pardo and Yuyan Cheng and Kimberlee Downey and Jope, {Richard S} and Eleonore Beurel",
year = "2014",
month = "1",
day = "1",
doi = "10.1016/j.pharmthera.2013.07.010",
language = "English",
volume = "141",
pages = "1--12",
journal = "Pharmacology and Therapeutics",
issn = "0163-7258",
publisher = "Elsevier Inc.",
number = "1",

}

TY - JOUR

T1 - Glycogen synthase kinase-3 inhibitors

T2 - Rescuers of cognitive impairments

AU - King, Margaret K.

AU - Pardo, Marta

AU - Cheng, Yuyan

AU - Downey, Kimberlee

AU - Jope, Richard S

AU - Beurel, Eleonore

PY - 2014/1/1

Y1 - 2014/1/1

N2 - 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.

AB - 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.

KW - Alzheimer's disease

KW - Fragile X syndrome

KW - Glycogen synthase kinase-3

KW - Learning

KW - Lithium

KW - LTP

UR - http://www.scopus.com/inward/record.url?scp=84890552198&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84890552198&partnerID=8YFLogxK

U2 - 10.1016/j.pharmthera.2013.07.010

DO - 10.1016/j.pharmthera.2013.07.010

M3 - Article

VL - 141

SP - 1

EP - 12

JO - Pharmacology and Therapeutics

JF - Pharmacology and Therapeutics

SN - 0163-7258

IS - 1

ER -