PMID- 38301932
OWN - NLM
STAT- MEDLINE
DCOM- 20240311
LR  - 20240311
IS  - 1872-7549 (Electronic)
IS  - 0166-4328 (Linking)
VI  - 463
DP  - 2024 Apr 12
TI  - Mitophagy activation by rapamycin enhances mitochondrial function and cognition 
      in 5xFAD mice.
PG  - 114889
LID - S0166-4328(24)00045-7 [pii]
LID - 10.1016/j.bbr.2024.114889 [doi]
AB  - Alzheimer's disease (AD) is the most prevalent form of dementia, characterized by 
      severe mitochondrial dysfunction, which is an intracellular process that is 
      significantly compromised in the early stages of AD. Mitophagy, the selective 
      removal of damaged mitochondria, is a potential therapeutic strategy for AD. 
      Rapamycin, a mammalian target of rapamycin (mTOR) inhibitor, augmented autophagy 
      and mitigated cognitive impairment. Our study revealed that rapamycin enhances 
      cognitive function by activating mitophagy, alleviating neuronal loss, and 
      improving mitochondrial dysfunction in 5 xFAD mice. Interestingly, the 
      neuroprotective effect of rapamycin in AD were negated by treatment with 3-MA, a 
      mitophagy inhibitor. Overall, our findings suggest that rapamycin ameliorates 
      cognitive impairment in 5 xFAD mice via mitophagy activation and its downstream 
      PINK1-Parkin pathway, which aids in the clearance of amyloid-beta (Abeta) and damaged 
      mitochondria. This study reveals a novel mechanism involving mitophagy regulation 
      underlying the therapeutic effect of rapamycin in AD. This study provides new 
      insights and therapeutic targets for rapamycin in the treatment of AD. However, 
      there are still some shortcomings in this topic; if we can further knock out the 
      PINK1/Parkin gene in animals or use siRNA technology, we can further confirm the 
      experimental results.
CI  - Copyright (c) 2024 The Authors. Published by Elsevier B.V. All rights reserved.
FAU - Zheng, Wenrong
AU  - Zheng W
AD  - School of Pharmacy, Fujian Medical University, Fuzhou 350122, China.
FAU - Li, Kualiang
AU  - Li K
AD  - School of Pharmacy, Fujian Medical University, Fuzhou 350122, China; Fujian 
      Institute of Microbiology, Fuzhou 350007, China.
FAU - Zhong, Meihua
AU  - Zhong M
AD  - School of Pharmacy, Fujian Medical University, Fuzhou 350122, China.
FAU - Wu, Kejun
AU  - Wu K
AD  - Department of Endocrinology and Metabolism, Fujian Medical University Union 
      Hospital, Fuzhou 350001, China.
FAU - Zhou, Lele
AU  - Zhou L
AD  - School of Pharmacy, Fujian Medical University, Fuzhou 350122, China.
FAU - Huang, Jie
AU  - Huang J
AD  - Fujian Institute of Microbiology, Fuzhou 350007, China.
FAU - Liu, Libin
AU  - Liu L
AD  - Department of Endocrinology and Metabolism, Fujian Medical University Union 
      Hospital, Fuzhou 350001, China.
FAU - Chen, Zhou
AU  - Chen Z
AD  - School of Pharmacy, Fujian Medical University, Fuzhou 350122, China. Electronic 
      address: chenzhou@fjmu.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20240201
PL  - Netherlands
TA  - Behav Brain Res
JT  - Behavioural brain research
JID - 8004872
RN  - W36ZG6FT64 (Sirolimus)
RN  - EC 2.3.2.27 (Ubiquitin-Protein Ligases)
SB  - IM
MH  - Mice
MH  - Animals
MH  - Mitophagy
MH  - Sirolimus/pharmacology
MH  - *Alzheimer Disease/metabolism
MH  - Mitochondria/metabolism
MH  - Cognition
MH  - *Mitochondrial Diseases
MH  - Ubiquitin-Protein Ligases/genetics
MH  - Mammals/metabolism
OTO - NOTNLM
OT  - 5xFAD mice
OT  - Cognitive impairment
OT  - Mitochondrial dysfunction
OT  - Mitophagy
OT  - Rapamycin
COIS- Declaration of Competing Interest The authors have no conflict of interests to 
      declare.
EDAT- 2024/02/02 00:42
MHDA- 2024/03/11 06:44
CRDT- 2024/02/01 19:30
PHST- 2023/11/03 00:00 [received]
PHST- 2024/01/20 00:00 [revised]
PHST- 2024/01/29 00:00 [accepted]
PHST- 2024/03/11 06:44 [medline]
PHST- 2024/02/02 00:42 [pubmed]
PHST- 2024/02/01 19:30 [entrez]
AID - S0166-4328(24)00045-7 [pii]
AID - 10.1016/j.bbr.2024.114889 [doi]
PST - ppublish
SO  - Behav Brain Res. 2024 Apr 12;463:114889. doi: 10.1016/j.bbr.2024.114889. Epub 
      2024 Feb 1.