The trilateral interactions between mammalian target of rapamycin (mTOR) signaling, the circadian clock, and psychiatric disorders: an emerging model.
The trilateral interactions between mammalian target of rapamycin (mTOR) signaling, the circadian clock, and psychiatric disorders: an emerging model.
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DOI：
10.1038/s41398-022-02120-8
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发表时间：
2022-08-31
影响因子：
6.8
通讯作者：
Cao, Ruifeng
中科院分区：
文献类型：
--
作者：
Singla, Rubal;Mishra, Abhishek;Cao, Ruifeng
生理和行为的昼夜节律（~24小时）在进化上是保守的，几乎在所有生物体中都存在。这些节律是由所谓的“时钟基因/蛋白质”的日常振荡活动内源性驱动的，这些基因/蛋白质广泛分布在哺乳动物的大脑中。哺乳动物（mechanistic）靶雷帕霉素（mTOR）信号传导是一个基本的细胞内信号转导级联，控制重要的神经元过程，包括神经发育、突触可塑性、代谢和衰老。mTOR通路的失调与包括自闭症谱系障碍（ASD）和情绪障碍（MD）在内的精神疾病有关，在这些疾病中，患者经常表现出日常生理节律紊乱和大脑中昼夜节律基因表达异常。最近的研究发现，mTOR信号的活动受到生物钟的暂时控制，并在多个系统中表现出强大的昼夜节律振荡。同时，mTOR信号调节中枢和外周生物钟的基本特性，包括周期长度、夹带和同步。尽管潜在的机制仍有待充分阐明，但越来越多的临床和临床前证据支持mTOR信号、生物钟和精神疾病之间存在显著的串扰。在此，我们回顾了三方相互作用的最新进展，并提出了mTOR信号、生物钟和精神疾病（重点是ASD和MD）之间的“相互作用三角”模型。
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).
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影响因子：
16.2
作者：
Cao R;Robinson B;Xu H;Gkogkas C;Khoutorsky A;Alain T;Yanagiya A;Nevarko T;Liu AC;Amir S;Sonenberg N
通讯作者：
Sonenberg N
影响因子：
64.8
作者：
Autry, Anita E.;Adachi, Megunai;Nosyreva, Elena;Na, Elisa S.;Los, Maarten F.;Cheng, Peng-fei;Kavalali, Ege T.;Monteggia, Lisa M.
通讯作者：
Monteggia, Lisa M.
影响因子：
2.5
作者：
Butcher, GQ;Lee, BY;Obrietan, K
通讯作者：
Obrietan, K
影响因子：
25
作者：
Cao, Ruifeng;Gkogkas, Christos G.;de Zavalia, Nuria;Blum, Ian D.;Yanagiya, Akiko;Tsukumo, Yoshinori;Xu, Haiyan;Lee, Choogon;Storch, Kai-Florian;Liu, Andrew C.;Amir, Shimon;Sonenberg, Nahum
通讯作者：
Sonenberg, Nahum
影响因子：
3.1
作者：
Braam, Wiebe;Ehrhart, Friederike;Curfs, Leopold
通讯作者：
Curfs, Leopold