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Glycogen synthase kinase‐3β, mood stabilizers, and neuroprotection
Author(s) -
Li Xiaohua,
Bijur Gautam N,
Jope Richard S
Publication year - 2002
Publication title -
bipolar disorders
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.285
H-Index - 129
eISSN - 1399-5618
pISSN - 1398-5647
DOI - 10.1034/j.1399-5618.2002.40201.x
Subject(s) - gsk 3 , neuroprotection , glycogen synthase , gsk3b , mood , neuroscience , atp synthase , medicine , glycogen , kinase , chemistry , pharmacology , endocrinology , psychology , enzyme , biochemistry , psychiatry
Glycogen synthase kinase‐3β (GSK‐3β) is a central component in many critical intracellular signaling mechanisms. These include the phosphatidylinositol 3‐kinase/Akt cell survival pathway, which inhibits GSK‐3β activity. GSK‐3β itself inhibits the activation of several transcription factors, which are important cell survival factors, such as heat shock factor 1. These factors likely contribute to the recent revelation that GSK‐3β is a pro‐apoptotic enzyme. Recently, lithium has been identified as a selective and direct inhibitor of GSK‐3β. Based on these findings, we have proposed that part of the neuroprotectant properties of lithium is due to its ability to inhibit GSK‐3β, and thus block the facilitation of apoptosis produced by GSK‐3β. Since several anticonvulsants recently have been shown to be effective mood stabilizers, we examined if these agents are capable of protecting cells from GSK‐3β‐facilitated apoptosis. In addition to lithium, both valproic acid and lamotrigine, but not carbamazepine, provided protection from GSK‐3β‐facilitated apoptosis in human neuroblastoma SH‐SY5Y cells. These results demonstrate that several drugs therapeutic for bipolar disorder can provide neuroprotection by inhibiting the pro‐apoptotic effects of GSK‐3β, providing new evidence that dysregulation of GSK‐3β may contribute to the pathophysiology of bipolar disorder.