Small molecule modifiers of circadian clocks.

Small molecule modifiers of circadian clocks.
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DOI:
10.1007/s00018-012-1207-y
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发表时间:
2013-08
影响因子:
8
通讯作者:
Takahashi, Joseph S.
Takahashi, Joseph S.
中科院分区:
生物学1区
文献类型:
--
作者:
Chen, Zheng;Yoo, Seung-Hee;Takahashi, Joseph S.

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生物钟协调基本生理和行为过程的24小时振荡,以响应日常环境变化。这些时钟在恒定的条件下非常精确,但对复位信号的响应非常灵敏。随着核心振荡器的分子组成基本确定,最近的研究越来越多地集中在时钟修改机制/分子上。特别是,小分子修饰剂,内在的或外在的,正在成为强大的工具,了解基本的时钟生物学,以及开发推定的治疗药物的时钟相关的疾病。在这篇综述中,我们将重点关注能够改变生物钟的周期、相位或振幅的合成化合物,特别强调哺乳动物的生物钟。我们将讨论在基础和转化研究中利用这些小分子修饰剂的潜力。
Circadian clocks orchestrate 24-h oscillations of essential physiological and behavioral processes in response to daily environmental changes. These clocks are remarkably precise under constant conditions yet highly responsive to resetting signals. With the molecular composition of the core oscillator largely established, recent research has increasingly focused on clock modifying mechanisms/molecules. In particular, small-molecule modifiers, intrinsic or extrinsic, are emerging as powerful tools for understanding basic clock biology as well as developing putative therapeutic agents for clock-associated diseases. In this review, we will focus on synthetic compounds capable of modifying the period, phase or amplitude of circadian clocks, with particular emphasis on the mammalian clock. We will discuss the potential of exploiting these small-molecule modifiers in both basic and translational research.
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