The DOI matches its Crossref record; 44 of the 44 references it cites were found in a registry or an index.
Selective small‐molecule inhibitors of glycogen synthase kinase‐3 activity protect primary neurones from death
Abstract
The phosphatidylinositol 3‐kinase (PI 3‐kinase)/protein kinase B (PKB; also known as Akt) signalling pathway is recognized as playing a central role in the survival of diverse cell types. Glycogen synthase kinase‐3 (GSK‐3) is a ubiquitously expressed serine/threonine protein kinase that is one of several known substrates of PKB. PKB phosphorylates GSK‐3 in response to insulin and growth factors, which inhibits GSK‐3 activity and leads to the modulation of multiple GSK‐3 regulated cellular processes. We show that the novel potent and selective small‐molecule inhibitors of GSK‐3; SB‐415286 and SB‐216763, protect both central and peripheral nervous system neurones in culture from death induced by reduced PI 3‐kinase pathway activity. The inhibition of neuronal death mediated by these compounds correlated with inhibition of GSK‐3 activity and modulation of GSK‐3 substrates tau and β‐catenin. Thus, in addition to the previously assigned roles of GSK‐3, our data provide clear pharmacological and biochemical evidence that selective inhibition of the endogenous pool of GSK‐3 activity in primary neurones is sufficient to prevent death, implicating GSK‐3 as a physiologically relevant principal regulatory target of the PI 3‐kinase/PKB neuronal survival pathway.
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Cites
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Cited by
GSK-3: tricks of the trade for a multi-tasking kinase
Doble, B. W., & Woodgett, J. R. (2003) · Journal of Cell Science · doi:10.1242/jcs.00384 · Cited by 2,084
GSK3 takes centre stage more than 20 years after its discovery
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Excitotoxicity and stroke: Identifying novel targets for neuroprotection
Lai, T. W., Zhang, S., & Wang, Y. T. (2014) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2013.11.006 · Cited by 1,106
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Metadata
- Authors
- Cross, D. A. E., Culbert, A. A., Chalmers, K. A., Facci, L., Skaper, S. D., & Reith, A. D.
- Venue
- Journal of Neurochemistry
- Publisher
- Wiley
- Published
- 2001-04
- Volume
- 77
- Issue
- 1
- Pages
- 94-102
- ISSN
- 0022-3042 (ISSN-L)
- 1471-4159
- OpenAlex
- W2012868552
- Cited by
- 377
- References
- 44
- FWCI
- 11.40
- Type
- journal article
- Language
- en
- Open access
- closed
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- Cross, D. A. E., Culbert, A. A., Chalmers, K. A., Facci, L., Skaper, S. D., & Reith, A. D. (2001). Selective small‐molecule inhibitors of glycogen synthase kinase‐3 activity protect primary neurones from death. Journal of Neurochemistry. https://doi.org/10.1046/j.1471-4159.2001.00251.x
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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