PMID- 35604830
OWN - NLM
STAT- MEDLINE
DCOM- 20220608
LR  - 20230824
IS  - 1945-4589 (Electronic)
IS  - 1945-4589 (Linking)
VI  - 14
IP  - 10
DP  - 2022 May 23
TI  - MRTF-A-mediated protection against amyloid-beta-induced neuronal injury correlates 
      with restoring autophagy via miR-1273g-3p/mTOR axis in Alzheimer models.
PG  - 4305-4325
LID - 10.18632/aging.203883 [doi]
AB  - Myocardia-Related Transcription Factors-A (MRTF-A), which is enriched in the 
      hippocampus and cerebral cortex, has been shown to have a protective function 
      against ischemia hypoxia-induced neuronal apoptosis. However, the function of 
      MRTF-A on beta-amyloid peptide (Abeta)-induced neurotoxicity and autophagy dysfunction 
      in Alzheimer's disease is still unclear. This study shows that the expression of 
      MRTF-A in the hippocampus of Tg2576 transgenic mice is reduced, and the 
      overexpression of MRTF-A mediated by lentiviral vectors carrying MRTF-A 
      significantly reduces the accumulation of hippocampal beta-amyloid peptide and 
      reduces cognition defect. Overexpression of MRTF-A inhibits neuronal apoptosis, 
      increases the protein levels of microtubule-associated protein 1 light chain 3-II 
      (MAP1LC3/LC3-II) and Beclin1, reduces the accumulation of SQSTM1/p62 protein, and 
      promotes autophagosomes-Lysosomal fusion in vivo and in vitro. Microarray 
      analysis and bioinformatics analysis show that MRTF-A reverses Abeta-induced 
      autophagy impairment by up-regulating miR-1273g-3p level leading to negative 
      regulation of the mammalian target of rapamycin (mTOR), which is confirmed in 
      Abeta(1-42)-treated SH-SY5Y cells. Further, overexpression of MRTF-A reduces 
      Abeta(1-42)-induced neuronal apoptosis. And the effect was abolished by miR-1273g-3p 
      inhibitor or MHY1485 (mTOR agonist), indicating that the protection of MRTF-A on 
      neuronal damage is through targeting miR-1273g-3p/mTOR axis. Targeting this 
      signaling may be a promising approach to protect against Abeta-induced neuronal 
      injury.
FAU - Zhang, Wei
AU  - Zhang W
AD  - Affiliated Wuhan Resources and Wisco General Hospital, University of Science and 
      Technology, Wuhan, Hubei, China.
FAU - Yang, Yuewang
AU  - Yang Y
AD  - College of Pharmacy, Shanghai University of Medicine and Health Sciences, 
      Shanghai, China.
FAU - Xiang, Zifei
AU  - Xiang Z
AD  - College of Medicine, Wuhan University of Science and Technology, Wuhan, Hubei, 
      China.
FAU - Cheng, Jinping
AU  - Cheng J
AD  - Affiliated Wuhan Resources and Wisco General Hospital, University of Science and 
      Technology, Wuhan, Hubei, China.
FAU - Yu, Zhijun
AU  - Yu Z
AD  - College of Medicine, Wuhan University of Science and Technology, Wuhan, Hubei, 
      China.
FAU - Wang, Wen
AU  - Wang W
AD  - Affiliated Wuhan Resources and Wisco General Hospital, University of Science and 
      Technology, Wuhan, Hubei, China.
FAU - Hu, Ling
AU  - Hu L
AD  - College of Medicine, Wuhan University of Science and Technology, Wuhan, Hubei, 
      China.
FAU - Ma, Fuyun
AU  - Ma F
AD  - College of Pharmacy, Shanghai University of Medicine and Health Sciences, 
      Shanghai, China.
FAU - Deng, Youping
AU  - Deng Y
AD  - Bioinformatics Core Department of Quantitative Health Sciences, John A. Burns 
      School of Medicine, University of Hawaii, Honolulu, HI 96813, USA.
FAU - Jin, Zhigang
AU  - Jin Z
AD  - Affiliated Wuhan Resources and Wisco General Hospital, University of Science and 
      Technology, Wuhan, Hubei, China.
FAU - Hu, Xiamin
AU  - Hu X
AD  - College of Pharmacy, Shanghai University of Medicine and Health Sciences, 
      Shanghai, China.
LA  - eng
GR  - P20 GM103466/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220523
PL  - United States
TA  - Aging (Albany NY)
JT  - Aging
JID - 101508617
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (MicroRNAs)
RN  - 0 (Mrtfa protein, mouse)
RN  - 0 (Trans-Activators)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Alzheimer Disease/genetics/metabolism
MH  - *Amyloid beta-Peptides/adverse effects/metabolism
MH  - Animals
MH  - Apoptosis/genetics
MH  - *Autophagy/genetics
MH  - *Hippocampus/injuries/metabolism
MH  - Humans
MH  - Mammals/metabolism
MH  - Mice
MH  - Mice, Transgenic
MH  - *MicroRNAs/metabolism
MH  - Neuroblastoma
MH  - Neurons/metabolism
MH  - TOR Serine-Threonine Kinases
MH  - *Trans-Activators/biosynthesis/genetics
PMC - PMC9186769
OTO - NOTNLM
OT  - Alzheimer's disease
OT  - MRTF-A
OT  - autophagy
OT  - mTOR
OT  - miR-1273g-3p
COIS- CONFLICTS OF INTEREST: The authors declare that they have no conflicts of 
      interest.
EDAT- 2022/05/24 06:00
MHDA- 2022/06/09 06:00
PMCR- 2022/05/31
CRDT- 2022/05/23 12:53
PHST- 2021/03/22 00:00 [received]
PHST- 2021/12/07 00:00 [accepted]
PHST- 2022/05/24 06:00 [pubmed]
PHST- 2022/06/09 06:00 [medline]
PHST- 2022/05/23 12:53 [entrez]
PHST- 2022/05/31 00:00 [pmc-release]
AID - 203883 [pii]
AID - 10.18632/aging.203883 [doi]
PST - ppublish
SO  - Aging (Albany NY). 2022 May 23;14(10):4305-4325. doi: 10.18632/aging.203883. Epub 
      2022 May 23.