Circadian neurogenetics and its implications in neurophysiology, behavior, and chronomedicine

The circadian rhythm affects multiple physiological processes, and disruption of the circadian system can be involved in a range of disease-related pathways. The genetic underpinnings of the circadian rhythm have been well-studied in model organisms. Significant progress has been made in understanding how clock genes affect the physiological functions of the nervous system. In addition, circadian timing is becoming a key factor in improving drug efficacy and reducing drug toxicity. The circadian biology of the target cell determines how the organ responds to the drug at a specific time of day, thus regulating pharmacodynamics. The current review brings together recent advances that have begun to unravel the molecular mechanisms of how the circadian clock affects neurophysiological and behavioral processes associated with human brain diseases. We start with a brief description of how the ubiquitous circadian rhythms are regulated at the genetic, cellular, and neural circuit levels, based on knowledge derived from extensive research on model organisms. We then summarize the latest findings from genetic studies of human brain disorders, focusing on the role of human clock gene variants in these diseases. Lastly, we discuss the impact of common dietary factors and medications on human circadian rhythms and advocate for a broader application of the concept of chronomedicine. •The cellular circadian clock is endogenously driven by transcription-translation feedback loops.•The suprachiasmatic nucleus (SCN) is the master circadian pacemaker in mammals.•Circadian rhythms are found in various extra-SCN brain regions and regulate neurophysiology and behavior.•Disruption of circadian rhythms and clock gene variations are associated with many human brain diseases.•The concept of chronomedicine and chronotherapy should be widely applied to promote health and treat diseases.