FRIDAY, Feb. 17 (HealthDay News) -- The beneficial effects of lithium for the treatment of bipolar disorder may be due to its degradation of the Rev-erb-alpha receptor, a negative regulator of circadian clock gene expression, according to a study published in the Feb. 17 issue of Science. The discovery may provide a molecular basis for how lithium works to treat bipolar disorder, which is associated with altered circadian rhythm.
Mitchell A. Lazar, M.D., Ph.D., of the University of Pennsylvania School of Medicine in Philadelphia, and colleagues analyzed cultured cells exposed to lithium and found that GSK3-beta phosphorylated and stabilized the orphan nuclear receptor Rev-erb-alpha, a negative component of the circadian clock.
Treatment of cells with lithium not only led to degradation of Rev-erb-alpha but also to activation of clock gene Bmal1. "A form of Rev-erb-alpha that is insensitive to lithium interferes with the expression of circadian genes. Control of Rev-erb-alpha protein stability is thus a critical component of the peripheral clock and a biological target of lithium therapy," the authors conclude.
Abstract
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