Dataset Information

MRTF-A-mediated protection against amyloid-β-induced neuronal injury correlates with restoring autophagy via miR-1273g-3p/mTOR axis in Alzheimer models.

ABSTRACT: 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 β-amyloid peptide (Aβ)-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 β-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 Aβ-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 Aβ_1-42-treated SH-SY5Y cells. Further, overexpression of MRTF-A reduces Aβ_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 Aβ-induced neuronal injury.

SUBMITTER: Zhang W

PROVIDER: S-EPMC9186769 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

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MRTF-A-mediated protection against amyloid-β-induced neuronal injury correlates with restoring autophagy via miR-1273g-3p/mTOR axis in Alzheimer models.

Zhang Wei W Yang Yuewang Y Xiang Zifei Z Cheng Jinping J Yu Zhijun Z Wang Wen W Hu Ling L Ma Fuyun F Deng Youping Y Jin Zhigang Z Hu Xiamin X

Aging 20220523 10

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 β-amyloid peptide (Aβ)-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 ...[more]

PMID: 35604830

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Dataset Information

MRTF-A-mediated protection against amyloid-β-induced neuronal injury correlates with restoring autophagy via miR-1273g-3p/mTOR axis in Alzheimer models.

Publications

MRTF-A-mediated protection against amyloid-β-induced neuronal injury correlates with restoring autophagy via miR-1273g-3p/mTOR axis in Alzheimer models.

Similar Datasets

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