2. Academic Validation
  3. Melatonin ameliorates cognitive deficits through improving mitophagy in a mouse model of Alzheimer's disease

Melatonin ameliorates cognitive deficits through improving mitophagy in a mouse model of Alzheimer's disease

  • J Pineal Res. 2021 Dec;71(4):e12774. doi: 10.1111/jpi.12774.
Chongyang Chen 1,  Chao Yang 2 3,  Jing Wang 4,  Xi Huang 5,  Haitao Yu 4,  Shangming Li 4,  Shupeng Li 6,  Zaijun Zhang 7,  Jianjun Liu 4,  Xifei Yang 4,  Gong-Ping Liu 1 8
Affiliations

Affiliations

  • 1 Department of Pathophysiology, School of Basic Medicine and the Collaborative Innovation Center for Brain Science, Key Laboratory of Ministry of Education of China and Hubei Province for Neurological Disorders, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • 2 Cognitive Impairment Ward of Neurology Department, the Third Affiliated Hospital of Shenzhen University Medical College, Shenzhen, Guangdong, China.
  • 3 Department of Neurology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
  • 4 Key Laboratory of Modern Toxicology of Shenzhen, Shenzhen Medical Key Discipline of Health Toxicology (2020-2024), Shenzhen Center for Disease Control and Prevention, Shenzhen, China.
  • 5 Department of Neurology, Shenzhen People's Hospital (First Affiliated Hospital of Southern University of Science and Technology), Second Clinical College, Jinan University, Shenzhen, Guangdong Province, China.
  • 6 School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen, China.
  • 7 Institute of New Drug Research and Guangzhou, Key Laboratory of Innovative Chemical Drug Research in Cardio-cerebrovascular Diseases, Jinan University College of Pharmacy, Guangzhou, China.
  • 8 Co-innovation Center of Neurodegeneration, Nantong University, Nantong, JS, China.
PMID: 34617321 DOI: 10.1111/jpi.12774
Abstract

While melatonin is known to have protective effects in mitochondria-related diseases, aging, and neurodegenerative disorders, there is poor understanding of the effects of melatonin treatment on Mitophagy in Alzheimer's disease (AD). We used proteomic analysis to investigate the effects and underlying molecular mechanisms of oral melatonin treatment on Mitophagy in the hippocampus of 4-month-old wild-type mice versus age-matched 5 × FAD mice, an animal model of AD. 5 × FAD mice showed disordered Mitophagy and mitochondrial dysfunction as revealed by increased mtDNA, mitochondrial marker proteins and MDA production, decreased electron transport chain proteins and ATP levels, and co-localization of Lamp1 and Tomm20. Melatonin treatment reversed the abnormal expression of proteins in the signaling pathway of lysosomes, pathologic phagocytosis of microglia, and mitochondrial energy metabolism. Moreover, melatonin restored Mitophagy by improving mitophagosome-lysosome fusion via Mcoln1, and thus, ameliorated mitochondrial functions, attenuated Aβ pathology, and improved cognition. Concurrent treatment with chloroquine and melatonin blocked the positive behavioral and biochemical effects of administration with melatonin alone. Taken in concert, these results suggest that melatonin reduces AD-related deficits in Mitophagy such that the drug should be considered as a therapeutic candidate for the treatment of AD.

Keywords

Alzheimer's disease; melatonin; mitochondrial function; mitophagy; proteomic.

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