Tags

Type your tag names separated by a space and hit enter

Role of glycogen synthase kinase-3 in Alzheimer's disease pathogenesis and glycogen synthase kinase-3 inhibitors.
Expert Rev Neurother. 2010 May; 10(5):703-10.ER

Abstract

Glycogen synthase kinase (GSK)-3 has been proposed as the link between the two histopathological hallmarks of Alzheimer's disease, the extracellular senile plaques composed of beta-amyloid and the intracellular neurofibrillary tangles formed from hyperphosphorylated tau. Thus, GSK-3 is one of the main tau kinases and it modifies several sites of the tau protein present in neurofibrillary tangles. Furthermore, GSK-3 is able to modulate the generation of amyloid-beta, as well as to respond to this peptide. In several transgenic models, overexpression of GSK-3 has been associated with neuronal death, tau hyperphosphorylation and a decline in cognitive performance. Lithium, a widely used drug for affective disorders, inhibits GSK-3 at therapeutically relevant concentrations and it has been demonstrated that this is able to prevent tau phosphorylation. In the present review, we summarize all these data and discuss the potential of GSK-3 inhibitors for Alzheimer's disease therapy, as well as some of their potential problems.

Links

Publisher Full Text
Aggregator Full Text

Authors+Show Affiliations

Avila J
Centro de Biología Molecular Severo Ochoa, CSIC/UAM, Nicolás Cabrera 1, Universidad Autónoma de Madrid, Cantoblanco, Madrid, Spain. javila@cbm.uam.es
Wandosell F
No affiliation info available
Hernández F
No affiliation info available

MeSH

Alzheimer DiseaseAnimalsDisease Models, AnimalEnzyme InhibitorsGlycogen Synthase Kinase 3HumansMiceModels, MolecularNeurofibrillary TanglesPlaque, Amyloidtau Proteins

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20420491

Citation

Avila, Jesús, et al. "Role of Glycogen Synthase Kinase-3 in Alzheimer's Disease Pathogenesis and Glycogen Synthase Kinase-3 Inhibitors." Expert Review of Neurotherapeutics, vol. 10, no. 5, 2010, pp. 703-10.
Avila J, Wandosell F, Hernández F. Role of glycogen synthase kinase-3 in Alzheimer's disease pathogenesis and glycogen synthase kinase-3 inhibitors. Expert Rev Neurother. 2010;10(5):703-10.
Avila, J., Wandosell, F., & Hernández, F. (2010). Role of glycogen synthase kinase-3 in Alzheimer's disease pathogenesis and glycogen synthase kinase-3 inhibitors. Expert Review of Neurotherapeutics, 10(5), 703-10. https://doi.org/10.1586/ern.10.40
Avila J, Wandosell F, Hernández F. Role of Glycogen Synthase Kinase-3 in Alzheimer's Disease Pathogenesis and Glycogen Synthase Kinase-3 Inhibitors. Expert Rev Neurother. 2010;10(5):703-10. PubMed PMID: 20420491.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Role of glycogen synthase kinase-3 in Alzheimer's disease pathogenesis and glycogen synthase kinase-3 inhibitors. AU - Avila,Jesús, AU - Wandosell,Francisco, AU - Hernández,Félix, PY - 2010/4/28/entrez PY - 2010/4/28/pubmed PY - 2010/8/12/medline SP - 703 EP - 10 JF - Expert review of neurotherapeutics JO - Expert Rev Neurother VL - 10 IS - 5 N2 - Glycogen synthase kinase (GSK)-3 has been proposed as the link between the two histopathological hallmarks of Alzheimer's disease, the extracellular senile plaques composed of beta-amyloid and the intracellular neurofibrillary tangles formed from hyperphosphorylated tau. Thus, GSK-3 is one of the main tau kinases and it modifies several sites of the tau protein present in neurofibrillary tangles. Furthermore, GSK-3 is able to modulate the generation of amyloid-beta, as well as to respond to this peptide. In several transgenic models, overexpression of GSK-3 has been associated with neuronal death, tau hyperphosphorylation and a decline in cognitive performance. Lithium, a widely used drug for affective disorders, inhibits GSK-3 at therapeutically relevant concentrations and it has been demonstrated that this is able to prevent tau phosphorylation. In the present review, we summarize all these data and discuss the potential of GSK-3 inhibitors for Alzheimer's disease therapy, as well as some of their potential problems. SN - 1744-8360 UR - https://www.unboundmedicine.com/medline/citation/20420491/Role_of_glycogen_synthase_kinase_3_in_Alzheimer's_disease_pathogenesis_and_glycogen_synthase_kinase_3_inhibitors_ L2 - https://www.tandfonline.com/doi/full/10.1586/ern.10.40 DB - PRIME DP - Unbound Medicine ER -