In mammals, the apex of this system is the suprachiasmatic nucleus (SCN) of the hypothalamus, which is considered the central or master clock ( Ralph et al., 1990 Reppert and Weaver, 2002). This clock is self-sustainable through an elaborate cooperation of genetic components and is hierarchically organized into a circadian timing system. These evolutionarily well-conserved rhythms arise from an intrinsic timekeeping system known as the “circadian clock”, which allows organisms to anticipate environmental cycling and coordinate biological processes. In this mini-review, we focus on recent discoveries of small molecules that pharmacologically modulate the core components of the circadian clock and their potential as preventive and/or therapeutic strategies for circadian clock-related neuropsychiatric diseases.Ĭircadian rhythms are ubiquitous biological oscillations with an approximate 24-h period. Importantly, circadian rhythm disruptions correlate with, and often precede, many symptoms of various neuropsychiatric disorders such as sleep disorders, affective disorders, addiction-related disorders, and neurodegeneration. These pharmaceutical approaches may include the development of new drugs to treat circadian clock-related disorders or combinational use with existing therapeutic strategies to improve efficacy via intrinsic clock-dependent mechanisms. Small molecules that target the molecular clock may present novel therapeutic strategies to treat chronic circadian rhythm-related diseases. As our understanding of these underlying mechanisms and their functional outputs has expanded, strategies have emerged to pharmacologically control the circadian molecular clock. Specifically, these rhythms are generated by two interlocking transcription/translation feedback loops of clock proteins. Since the first identification of mammalian circadian clock genes, numerous genetic and biochemical studies have revealed the molecular basis of these cell-autonomous and self-sustainable rhythms. Such periodicity is critical for homeostasis because disruption or misalignment of the intrinsic rhythms is associated with the onset and progression of various human diseases and often directly leads to pathological states. 3College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu, South KoreaĬircadian rhythms regulate many biological processes and play fundamental roles in behavior, physiology, and metabolism.2Department of Brain and Cognitive Sciences, Scranton College, Ewha Womans University, Seoul, South Korea.
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