GSK3 inhibitors: development and therapeutic potential View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2004-06

AUTHORS

Philip Cohen, Michel Goedert

ABSTRACT

Key PointsIn the late 1970s, glycogen synthase kinase-3 (GSK3) was identified as a protein kinase that inactivates glycogen synthase, but was ignored as a drug target by the pharmaceutical industry until the mid-1990s, when its role in insulin signal transduction was clarified.Several potent inhibitors of GSK3 were identified in the late 1990s, and cell-based assays using these compounds indicated that they might have therapeutic potential for the treatment of diabetes. During the past year or so, very potent and more specific inhibitors of GSK3 have been introduced.GSK3 inhibitors have now been shown to be effective in normalizing blood glucose levels in animal models of type 2 diabetes, with their effects seeming to occur primarily through an increase in hepatic glycogen synthesis and a decrease in hepatic gluconeogenesis.GSK3 inhibitors might also have potential for neurodegenerative disorders, such as Alzheimer's disease. For example, there is recent evidence that GSK3 increases the production of β-amyloid — which has a key role in the pathogenesis of Alzheimer's disease — and that inhibition of GSK3 might reduce β-amyloid levels. More... »

PAGES

479-487

Journal

TITLE

Nature Reviews Drug Discovery

ISSUE

6

VOLUME

3

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/nrd1415

    DOI

    http://dx.doi.org/10.1038/nrd1415

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1051744913

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/15173837


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