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Modulation of autophagy by melatonin and its receptors: implications in brain disorders

Acta Pharmacologica Sinica volume 46, pages 525–538 (2025)Cite this article

Abstract

Autophagy plays a crucial role in maintaining neuronal homeostasis and function, and its disruption is linked to various brain diseases. Melatonin, an endogenous hormone that primarily acts through MT1 and MT2 receptors, regulates autophagy via multiple pathways. Growing evidence indicates that melatonin’s ability to modulate autophagy provides therapeutic and preventive benefits in brain disorders, including neurodegenerative and affective diseases. In this review, we summarize the key mechanisms by which melatonin affects autophagy and explore its therapeutic potential in the treatment of brain disorders.

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Fig. 1: Melatonin signaling pathways.
Fig. 2: Melatonin transcriptional regulation of autophagy.
Fig. 3: Schematic diagram of the melatonin regulation of autophagy.

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Acknowledgements

This work is supported by the Fundamental Research Funds for the Zhejiang Provincial Universities (226-2023-00013), the Starry Night Science Fund of Zhejiang University Shanghai Institute for Advanced Study (SN-ZJU-SIAS-0011), the National Natural Science Foundation of China (82173792), and the Jinhua Science and Technology Plan Projects (2023-3-170).

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  1. These authors contributed equally: Chen-ze Zhu, Gui-zhi Li

Authors and Affiliations

  1. Institute of Pharmacology & Toxicology, College of Pharmaceutical Sciences, Key Laboratory of Medical Neurobiology of the Ministry of Health of China, Zhejiang University, Hangzhou, 310058, China

    Chen-ze Zhu, Yang-yang Lu, Yue Li & Xiang-nan Zhang

  2. School of Pharmacy, Hangzhou Medical College, Hangzhou, 311399, China

    Gui-zhi Li & Hai-feng Lyu

  3. Jinhua Institute of Zhejiang University, Jinhua, 321299, China

    Xiang-nan Zhang

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  1. Chen-ze Zhu
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Contributions

CZZ and XNZ conceptualized the study. CZZ and GZL wrote the initial draft. HFL and YYL revised the manuscript. YL was responsible for creating figures and tables. XNZ supervised the article. All authors have read and agreed to the published version of the manuscript.

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Correspondence to Xiang-nan Zhang.

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Zhu, Cz., Li, Gz., Lyu, Hf. et al. Modulation of autophagy by melatonin and its receptors: implications in brain disorders. Acta Pharmacol Sin 46, 525–538 (2025). https://doi.org/10.1038/s41401-024-01398-2

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