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

Chen, Chongyang1,2; Yang, Chao3,4; Wang, Jing5; Huang, Xi6; Yu, Haitao5; Li, Shangming5; Li, Shupeng7; Zhang, Zaijun8; Liu, Jianjun5; Yang, Xifei5; Liu, Gong-Ping1,2,9

2021-10-01

10.1111/jpi.12774

JOURNAL OF PINEAL RESEARCH   影响因子和分区

0742-3098

1600-079X

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 x FAD mice, an animal model of AD. 5 x 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 A beta 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.

Alzheimer's disease melatonin mitochondrial function mitophagy proteomic

SCI

英语

其他

Natural Science Foundation of China[81673134,81870846] ; Ministry of Science and Technology of China[2016YFC13058001] ; Guangdong Provincial Key ST Program[2018B030336001] ; Key program of Shenzhen Basic Research[JCYJ20200108165353400] ; Sanming Project of Medicine in Shenzhen[SZSM201611090]

Endocrinology & Metabolism ; Neurosciences & Neurology ; Physiology

Endocrinology & Metabolism ; Neurosciences ; Physiology

WOS:000707396100001

WILEY

BIOLOGY & BIOCHEMISTRY

Web of Science

1.Huazhong Univ Sci & Technol, Tongji Med Coll, Sch Basic Med, Dept Pathophysiol, Wuhan 430030, Peoples R China
2.Huazhong Univ Sci & Technol, Tongji Med Coll, Collaborat Innovat Ctr Brain Sci, Key Lab,Minist Educ China & Hubei Prov Neurol Dis, Wuhan 430030, Peoples R China
3.Shenzhen Univ, Affiliated Hosp 3, Med Coll, Cognit Impairment Ward,Neurol Dept, Shenzhen, Guangdong, Peoples R China
4.Guangzhou Med Univ, Affiliated Hosp 1, Dept Neurol, Guangzhou, Peoples R China
5.Shenzhen Ctr Dis Control & Prevent, Shenzhen Med Key Discipline Hlth Toxicol 2020 202, Key Lab Modern Toxicol Shenzhen, Shenzhen, Peoples R China
6.Jinan Univ, Southern Univ Sci & Technol, Affiliated Hosp 1, Dept Neurol,Shenzhen Peoples Hosp,Clin Coll 2, Shenzhen, Guangdong, Peoples R China
7.Peking Univ, Shenzhen Grad Sch, Sch Chem Biol & Biotechnol, Shenzhen, Peoples R China
8.Jinan Univ, Coll Pharm, Inst New Drug Res & Guangzhou, Key Lab Innovat Chem Drug Res Cardio Cerebrovasc, Guangzhou, Peoples R China
9.Nantong Univ, Coinnovat Ctr Neurodegenerat, Nantong, JS, Peoples R China

Chen, Chongyang,Yang, Chao,Wang, Jing,et al. Melatonin ameliorates cognitive deficits through improving mitophagy in a mouse model of Alzheimer's disease[J]. JOURNAL OF PINEAL RESEARCH,2021.

Chen, Chongyang.,Yang, Chao.,Wang, Jing.,Huang, Xi.,Yu, Haitao.,...&Liu, Gong-Ping.(2021).Melatonin ameliorates cognitive deficits through improving mitophagy in a mouse model of Alzheimer's disease.JOURNAL OF PINEAL RESEARCH.

Chen, Chongyang,et al."Melatonin ameliorates cognitive deficits through improving mitophagy in a mouse model of Alzheimer's disease".JOURNAL OF PINEAL RESEARCH (2021).