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The trilateral interactions between mammalian target of rapamycin (mTOR) signaling, the circadian clock, and psychiatric disorders: an emerging model
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...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9433414/ https://www.ncbi.nlm.nih.gov/pubmed/36045116 http://dx.doi.org/10.1038/s41398-022-02120-8 |
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author | Singla, Rubal Mishra, Abhishek Cao, Ruifeng |
author_facet | Singla, Rubal Mishra, Abhishek Cao, Ruifeng |
author_sort | Singla, Rubal |
collection | PubMed |
description | 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). |
format | Online Article Text |
id | pubmed-9433414 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-94334142022-09-02 The trilateral interactions between mammalian target of rapamycin (mTOR) signaling, the circadian clock, and psychiatric disorders: an emerging model Singla, Rubal Mishra, Abhishek Cao, Ruifeng Transl Psychiatry Review Article 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). Nature Publishing Group UK 2022-08-31 /pmc/articles/PMC9433414/ /pubmed/36045116 http://dx.doi.org/10.1038/s41398-022-02120-8 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Review Article Singla, Rubal Mishra, Abhishek Cao, Ruifeng The trilateral interactions between mammalian target of rapamycin (mTOR) signaling, the circadian clock, and psychiatric disorders: an emerging model |
title | The trilateral interactions between mammalian target of rapamycin (mTOR) signaling, the circadian clock, and psychiatric disorders: an emerging model |
title_full | The trilateral interactions between mammalian target of rapamycin (mTOR) signaling, the circadian clock, and psychiatric disorders: an emerging model |
title_fullStr | The trilateral interactions between mammalian target of rapamycin (mTOR) signaling, the circadian clock, and psychiatric disorders: an emerging model |
title_full_unstemmed | The trilateral interactions between mammalian target of rapamycin (mTOR) signaling, the circadian clock, and psychiatric disorders: an emerging model |
title_short | The trilateral interactions between mammalian target of rapamycin (mTOR) signaling, the circadian clock, and psychiatric disorders: an emerging model |
title_sort | trilateral interactions between mammalian target of rapamycin (mtor) signaling, the circadian clock, and psychiatric disorders: an emerging model |
topic | Review Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9433414/ https://www.ncbi.nlm.nih.gov/pubmed/36045116 http://dx.doi.org/10.1038/s41398-022-02120-8 |
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