Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.26 (GSK)
 6,788 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Activation of GSK-3beta is presumed to be involved in various neurodegenerative diseases, including Alzheimer's disease (AD), which is characterized by memory disturbances during early stages of the disease. The normal function of GSK-3beta in adult brain is not well understood. Here, we analyzed the ability of heterozygote GSK-3beta knockout (GSK+/-) mice to form memories. In the Morris water maze (MWM), learning and memory performance of GSK+/- mice was no different from that of wild-type (WT) mice for the first 3 days of training. With continued learning on subsequent days, however, retrograde amnesia was induced in GSK+/- mice, suggesting that GSK+/- mice might be impaired in their ability to form long-term memories. In contextual fear conditioning (CFC), context memory was normally consolidated in GSK+/- mice, but once the original memory was reactivated, they showed reduced freezing, suggesting that GSK+/- mice had impaired memory reconsolidation. Biochemical analysis showed that GSK-3beta was activated after memory reactivation in WT mice. Intraperitoneal injection of a GSK-3 inhibitor before memory reactivation impaired memory reconsolidation in WT mice. These results suggest that memory reconsolidation requires activation of GSK-3beta in the adult brain.
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PMID:GSK-3beta is required for memory reconsolidation in adult brain. 1895 52

Glycogen synthase kinase-3beta (GSK-3beta) is a constitutively active kinase. Since its activation results in neurofibrillary tangle (NFT) deposits in aged and Alzheimer's disease (AD) brains, GSK-3beta may be inhibited under normal conditions but activated under pathological conditions. Given its link to NFT formation, we sought to determine whether GSK-3beta exists in the brain as a "pathological time bomb" that promotes disease development. To address this hypothesis, we analyzed GSK-3beta heterozygote (GSK+/-) mice, which express GSK-3beta at 50% wild-type levels. When tested in the Morris water maze test, GSK+/- mice surprisingly exhibited retrograde amnesia. Further analysis indicated that GSK+/- mice had impaired memory reconsolidation but normal memory consolidation. Therefore, we concluded that GSK-3beta activation is required for memory reconsolidation in the adult brain.
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PMID:Drug development targeting the glycogen synthase kinase-3beta (GSK-3beta)-mediated signal transduction pathway: role of GSK-3beta in adult brain. 1917 3