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Circadian rhythms: mechanisms and therapeutic implications.

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1
INSERM U776, Unité de Chronothérapie, Service de Cancérologie, Hôpital Paul Brousse et Université Paris XI, 94800 Villejuif, France. levi-f@vjf.inserm.fr

Abstract

The mammalian circadian system is organized in a hierarchical manner in that a central pacemaker in the suprachiasmatic nucleus (SCN) of the brain's hypothalamus synchronizes cellular circadian oscillators in most peripheral body cells. Fasting-feeding cycles accompanying rest-activity rhythms are the major timing cues in the synchronization of many, if not most, peripheral clocks, suggesting that the temporal coordination of metabolism and proliferation is a major task of the mammalian timing system. The inactivation of noxious food components by hepatic, intestinal, and renal detoxification systems is among the metabolic processes regulated in a circadian manner, with the understanding of the involved clock output pathways emerging. The rhythmic control of xenobiotic detoxification provides the molecular basis for the dosing time-dependence of drug toxicities and efficacy. This knowledge can in turn be used in improving or designing chronotherapeutics for the patients who suffer from many of the major human diseases.

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