Training the Circadian Clock, Clocking the Drugs, and Drugging the Clock to Prevent, Manage, and Treat Chronic Diseases.

Training the Circadian Clock, Clocking the Drugs, and Drugging the Clock to Prevent, Manage, and Treat Chronic Diseases.
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训练昼夜节律时钟,对药物进行时钟,并为时钟吸毒以预防,管理和治疗慢性疾病。

DOI:
10.1016/j.tips.2018.07.003
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发表时间:
2018-09
影响因子:
13.8
通讯作者:
Panda S
Panda S
中科院分区:
医学1区
文献类型:
--
作者:
Sulli G;Manoogian ENC;Taub PR;Panda S

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行为、生理和新陈代谢的日常节律是体内平衡的一个组成部分。这些节律是由内源性生物钟、环境光-暗、睡眠-活动和饮食-禁食周期之间的相互作用产生的。几乎整个灵长类基因组都以组织和位点特异性的方式显示日常表达节律。这些分子节律调节细胞和组织功能的几个关键方面,对公共卫生、疾病预防和疾病管理具有深远的影响。在现代社会中,夜间的光线会扰乱昼夜节律,从而进一步扰乱睡眠和禁食周期。虽然急性昼夜节律紊乱可能会导致短暂的不适或加剧慢性疾病,但慢性昼夜节律紊乱可能会增加多种疾病的风险。对昼夜节律的分子理解正在开辟新的治疗领域,使生物钟发挥核心作用。在这里,我们回顾了如何通过行为干预、给药时机和生物钟成分的药理学靶向来增强生物钟的最新进展,这些进展已经为包括代谢综合征和癌症在内的多种疾病提供了新的预防和治疗策略。
Daily rhythms in behavior, physiology, and metabolism are an integral part of homeostasis. These rhythms emerge from interactions among endogenous circadian clocks, ambient light-dark-, sleep-activity-, and eating-fasting cycles. Nearly the entire primate genome shows daily rhythms in expression in a tissue- and locus- specific manner. These molecular rhythms modulate several key aspects of cellular and tissue function with profound implications in public health, disease prevention and disease management. In modern societies light at night disrupts circadian rhythms which leads to further disruption of sleep and eating-fasting cycles. While acute circadian disruption may cause transient discomfort or exacerbate chronic diseases, chronic circadian disruption can enhance risks for numerous diseases. The molecular understanding of circadian rhythms is opening new therapeutic frontiers placing the circadian clock in a central role. Here we review recent advancements on how to enhance our circadian clock through behavioral interventions, timing of drug administration and pharmacological targeting of circadian clock components that are already providing new preventive and therapeutic strategies for several diseases including metabolic syndrome and cancer.
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