Rapamycin Activates Mitophagy and Alleviates Cognitive and Synaptic Plasticity Deficits in a Mouse Model of Alzheimer's Disease. (18th May 2021)

• Record Type: Journal Article
• Authors: Wang, Hui; Fu, Jingxuan; Xu, Xinxin; Yang, Zhuo; Zhang, Tao
• Editors: Anderson, Rozalyn M
• Is Part Of: Journals of gerontology. Volume 76:Number 10(2021)
• Page Start: 1707
• Page End: 1713
• Publication Date: 2021-05-18
• Subjects: Apoptosis -- Dementia -- Mitophagy -- Oxidative stress -- Rapamycin; Geriatrics -- Periodicals; Gerontology -- Periodicals; 618.97
• DOI: 10.1093/gerona/glab142
• Languages: English
• ISSNs: 1079-5006

Abstract

Abstract: Alzheimer's disease (AD) is a chronic neurodegenerative disease, which is characterized by cognitive and synaptic plasticity damage. Rapamycin is an activator of autophagy/mitophagy, which plays an important role in identifying and degrading damaged mitochondria. The aim of this study was to investigate the effect of rapamycin on cognitive and synaptic plasticity defects induced by AD, and further explore if the underlying mechanism was associated with mitophagy. The results show that rapamycin increases Parkin-mediated mitophagy and promotes fusion of mitophagosome and lysosome in the APP/PS1 mouse hippocampus. Rapamycin enhances learning and memory viability, synaptic plasticity, and the expression of synapse-related proteins, impedes cytochrome C-mediated apoptosis, decreases oxidative status, and recovers mitochondrial function in APP/PS1 mice. The data suggest that rapamycin effectively alleviates AD-like behaviors and synaptic plasticity deficits in APP/PS1 mice, which is associated with enhanced mitophagy. Our findings possibly uncover an important function of mitophagy in eliminating damaged mitochondria to attenuate AD-associated pathology.