The trilateral interactions between mammalian target of rapamycin (mTOR) signaling, the circadian clock, and psychiatric disorders: an emerging model

Research output: Contribution to journalReview articlepeer-review

1 Scopus citations

Abstract

Circadian (~24 h) rhythms in physiology and behavior are evolutionarily conserved and found in almost all living organisms. The rhythms are endogenously driven by daily oscillatory activities of so-called "clock genes/proteins", which are widely distributed throughout the mammalian brain. Mammalian (mechanistic) target of rapamycin (mTOR) signaling is a fundamental intracellular signal transduction cascade that controls important neuronal processes including neurodevelopment, synaptic plasticity, metabolism, and aging. Dysregulation of the mTOR pathway is associated with psychiatric disorders including autism spectrum disorders (ASD) and mood disorders (MD), in which patients often exhibit disrupted daily physiological rhythms and abnormal circadian gene expression in the brain. Recent work has found that the activities of mTOR signaling are temporally controlled by the circadian clock and exhibit robust circadian oscillations in multiple systems. In the meantime, mTOR signaling regulates fundamental properties of the central and peripheral circadian clocks, including period length, entrainment, and synchronization. Whereas the underlying mechanisms remain to be fully elucidated, increasing clinical and preclinical evidence support significant crosstalk between mTOR signaling, the circadian clock, and psychiatric disorders. Here, we review recent progress in understanding the trilateral interactions and propose an "interaction triangle" model between mTOR signaling, the circadian clock, and psychiatric disorders (focusing on ASD and MD).

Original languageEnglish (US)
Pages (from-to)355
Number of pages1
JournalTranslational psychiatry
Volume12
Issue number1
DOIs
StatePublished - Aug 31 2022

Bibliographical note

Publisher Copyright:
© 2022. The Author(s).

PubMed: MeSH publication types

  • Journal Article
  • Review
  • Research Support, N.I.H., Extramural

Fingerprint

Dive into the research topics of 'The trilateral interactions between mammalian target of rapamycin (mTOR) signaling, the circadian clock, and psychiatric disorders: an emerging model'. Together they form a unique fingerprint.

Cite this