Clock-enhancing small molecules and potential applications in chronic diseases and aging

Gabrielle F. Gloston, Seung Hee Yoo, Zheng (Jake) Chen

Research output: Contribution to journalReview articlepeer-review

50 Scopus citations


Normal physiological functions require a robust biological timer called the circadian clock. When clocks are dysregulated, misaligned, or dampened, pathological consequences ensue, leading to chronic diseases and accelerated aging. An emerging research area is the development of clock-targeting compounds that may serve as drug candidates to correct dysregulated rhythms and hence mitigate disease symptoms and age-related decline. In this review, we first present a concise view of the circadian oscillator, physiological networks, and regulatory mechanisms of circadian amplitude. Given a close association of circadian amplitude dampening and disease progression, clock-enhancing small molecules (CEMs) are of particular interest as candidate chronotherapeutics. A recent proof-of-principle study illustrated that the natural polymethoxylated flavonoid nobiletin directly targets the circadian oscillator and elicits robust metabolic improvements in mice. We describe mood disorders and aging as potential therapeutic targets of CEMs. Future studies of CEMs will shed important insight into the regulation and disease relevance of circadian clocks.

Original languageEnglish (US)
Article number100
JournalFrontiers in Neurology
Issue numberMAR
StatePublished - Mar 15 2017


  • Aging
  • Amplitude
  • Circadian clock
  • Metabolic disease
  • Mood disorder
  • Small molecules

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology


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