Glycogen synthase kinase 3: a drug target for CNS therapies.

Bhat RV ¹,

Budd Haeberlein SL ,

Avila J

Affiliations

1. AstraZeneca R & D, Södertälje, B213:231B, Sweden 151-85.
Authors
Bhat RV¹
(1 author)

ORCIDs linked to this article

Avila J | 0000-0002-6288-0571

Journal of Neurochemistry, 01 Jun 2004, 89(6):1313-1317
https://doi.org/10.1111/j.1471-4159.2004.02422.x PMID: 15189333

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Abstract

Abstract Glycogen synthase kinase3 (GSK3) is emerging as a prominent drug target in the CNS. The most exciting of the possibilities of GSK3 lies within the treatment of Alzheimer's disease (AD) where abnormal increases in GSK3 levels and activity have been associated with neuronal death, paired helical filament tau formation and neurite retraction as well as a decline in cognitive performance. Abnormal activity of GSK3 is also implicated in stroke. Lithium, a widely used drug for affective disorders, inhibits GSK3 at therapeutically relevant concentrations. Thus while the rationale remains testable, pharmaceutical companies are investing in finding a selective inhibitor of GSK3. In the present review, we summarize the properties of GSK3, and discuss the potential for such a therapy in AD, and other CNS disorders.

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Glycogen synthase kinase 3: a drug target for CNS therapies.

Affiliations

ORCIDs linked to this article

Abstract

Full text links

References

Nuclear export of NF-ATc enhanced by glycogen synthase kinase-3.

Regulation and localization of tyrosine216 phosphorylation of glycogen synthase kinase-3beta in cellular and animal models of neuronal degeneration.

Interactions between GSK3β and caspase signaling pathways during NGF deprivation induced cell death

Structural insights and biological effects of glycogen synthase kinase 3-specific inhibitor AR-A014418.

A sequence of cytoskeleton changes related to the formation of neurofibrillary tangles and neuropil threads.

Phosphorylation of the cAMP response element binding protein CREB by cAMP-dependent protein kinase A and glycogen synthase kinase-3 alters DNA-binding affinity, conformation, and increases net charge.

Selective small-molecule inhibitors of glycogen synthase kinase-3 activity protect primary neurones from death.

GSK-3: tricks of the trade for a multi-tasking kinase.

Glycogen synthase kinase 3: an emerging therapeutic target.

Effect of acute hypoglycemia on visual information processing in adults with type 1 diabetes mellitus.

Citations & impact

Impact metrics

Citations of article over time

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Smart citations by scite.ai
Explore citation contexts and check if this article has been supported or disputed.
https://scite.ai/reports/10.1111/j.1471-4159.2004.02422.x

Article citations

Glycogen synthase kinase 3 (GSK3) inhibition: a potential therapeutic strategy for Alzheimer's disease.

Parkinson's Disease and MicroRNAs: A Duel Between Inhibition and Stimulation of Apoptosis in Neuronal Cells.

Secondary Metabolites of Biscogniauxia: Distribution, Chemical Diversity, Bioactivity, and Implications of the Occurrence.

Targeted protein degradation might present a novel therapeutic approach in the fight against African trypanosomiasis.

Discovery of imidazole-based GSK-3β inhibitors for transdifferentiation of human mesenchymal stem cells to neurons: A potential single-molecule neurotherapeutic foresight.

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Glycogen synthase kinase 3: a drug target for CNS therapies.

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Interactions between GSK3β and caspase signaling pathways during NGF deprivation induced cell death

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