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 article

18 Citations (Scopus)

Abstract

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
Volume8
Issue numberMAR
DOIs
StatePublished - Mar 15 2017

Fingerprint

Circadian Clocks
Chronic Disease
Mood Disorders
Flavonoids
Disease Progression
Research
Pharmaceutical Preparations
Therapeutics
nobiletin

Keywords

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

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

Clock-enhancing small molecules and potential applications in chronic diseases and aging. / Gloston, Gabrielle F.; Yoo, Seung Hee; Chen, Zheng (Jake).

In: Frontiers in Neurology, Vol. 8, No. MAR, 100, 15.03.2017.

Research output: Contribution to journalReview article

Gloston, Gabrielle F. ; Yoo, Seung Hee ; Chen, Zheng (Jake). / Clock-enhancing small molecules and potential applications in chronic diseases and aging. In: Frontiers in Neurology. 2017 ; Vol. 8, No. MAR.
@article{508702335bb1469ab18832d65ff54829,
title = "Clock-enhancing small molecules and potential applications in chronic diseases and aging",
abstract = "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.",
keywords = "Aging, Amplitude, Circadian clock, Metabolic disease, Mood disorder, Small molecules",
author = "Gloston, {Gabrielle F.} and Yoo, {Seung Hee} and Chen, {Zheng (Jake)}",
year = "2017",
month = "3",
day = "15",
doi = "10.3389/fneur.2017.00100",
language = "English (US)",
volume = "8",
journal = "Frontiers in Neurology",
issn = "1664-2295",
publisher = "Frontiers Research Foundation",
number = "MAR",

}

TY - JOUR

T1 - Clock-enhancing small molecules and potential applications in chronic diseases and aging

AU - Gloston, Gabrielle F.

AU - Yoo, Seung Hee

AU - Chen, Zheng (Jake)

PY - 2017/3/15

Y1 - 2017/3/15

N2 - 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.

AB - 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.

KW - Aging

KW - Amplitude

KW - Circadian clock

KW - Metabolic disease

KW - Mood disorder

KW - Small molecules

UR - http://www.scopus.com/inward/record.url?scp=85016147680&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85016147680&partnerID=8YFLogxK

U2 - 10.3389/fneur.2017.00100

DO - 10.3389/fneur.2017.00100

M3 - Review article

C2 - 28360884

AN - SCOPUS:85016147680

VL - 8

JO - Frontiers in Neurology

JF - Frontiers in Neurology

SN - 1664-2295

IS - MAR

M1 - 100

ER -