Circadian rhythms in gene expression: Relationship to physiology, disease, drug disposition and drug action.

摘要

Circadian rhythms (24h cycles) are observed in virtually all aspects of mammalian function from expression of genes to complex physiological processes. The master clock is present in the suprachiasmatic nucleus (SCN) in the anterior part of the hypothalamus and controls peripheral clocks present in other parts of the body. Components of this core clock mechanism regulate the circadian rhythms in genome-wide mRNA expression, which in turn regulate various biological processes. Disruption of circadian rhythms can be either the cause or the effect of various disorders including metabolic syndrome, inflammatory diseases and cancer. Furthermore, circadian rhythms in gene expression regulate both the action and disposition of various drugs and affect therapeutic efficacy and toxicity based on dosing time. Understanding the regulation of circadian rhythms in gene expression plays an important role in both optimizing the dosing time for existing drugs and in the development of new therapeutics targeting the molecular clock.