Small Molecule Modulators of the Circadian Molecular Clock With Implications for Neuropsychiatric Diseases
- 주제(키워드) circadian rhythm , circadian clock , cryptochrome , REV-ERB , ROR , small molecule , circadian rhythm-related disease
- 주제(기타) Neurosciences
- 설명문(일반) [Cha, Hyo Kyeong; Lim, Hye Young; Son, Gi Hoon] Korea Univ, Dept Biomed Sci, Coll Med, Seoul, South Korea; [Chung, Sooyoung] Ewha Womans Univ, Dept Brain & Cognit Sci, Scranton Coll, Seoul, South Korea; [Jung, Jong-Wha] Kyungpook Natl Univ, Res Inst Pharmaceut Sci, Coll Pharm, Daegu, South Korea
- 관리정보기술 faculty
- 등재 SCIE, SCOPUS
- OA유형 gold, Green Published
- 발행기관 FRONTIERS MEDIA SA
- 발행년도 2019
- URI http://www.dcollection.net/handler/ewha/000000160400
- 본문언어 영어
- Published As http://dx.doi.org/10.3389/fnmol.2018.00496
- PubMed https://pubmed.ncbi.nlm.nih.gov/30718998
초록/요약
Circadian rhythms regulate many biological processes and play fundamental roles in behavior, physiology, and metabolism. 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. 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. Specifically, these rhythms are generated by two interlocking transcription/translation feedback loops of clock proteins. As our understanding of these underlying mechanisms and their functional outputs has expanded, strategies have emerged to pharmacologically control the circadian molecular clock. Small molecules that target the molecular clock may present novel therapeutic strategies to treat chronic circadian rhythm-related diseases. 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. 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. 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.
more