Research Paper Volume 12, Issue 20 pp 20728—20742
MicroRNA-338-5p alleviates neuronal apoptosis via directly targeting BCL2L11 in APP/PS1 mice
- 1 Department of Anesthesiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China
- 2 Department of Pediatrics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China
- 3 Department of Cardiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China
- 4 Department of Intensive Care Unit, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China
- 5 Laboratory of RNA and Major Diseases of Brain and Hearts, Sun Yat-sen University, Guangzhou 510120, China
- 6 Guangdong Province Key Laboratory of Brain Function and Disease, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China
Received: May 11, 2020 Accepted: August 1, 2020 Published: October 21, 2020https://doi.org/10.18632/aging.104005
How to Cite
Copyright: © 2020 Li et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
MicroRNAs have become pivotal modulators in the pathogenesis of Alzheimer’s disease. MiR-338-5p is associated with neuronal differentiation and neurogenesis, and expressed aberrantly in patients with cognitive dysfunction. However, its role and potential mechanism involved in Alzheimer’s disease remain to be elucidated. Herein, we showed that the expression of miR-338-5p decreased in APP/PS1 mice, accompanied by the elevation in the expression level of amyloid β, which indicated a reverse relationship between Alzheimer’s disease progression and miR-338-5p. In addition, lentiviral overexpression of miR-338-5p through intrahippocampal injection mitigated the amyloid plaque deposition and cognitive dysfunction in APP/PS1 mice, suggesting a protecting role of miR-338-5p against the development of Alzheimer’s disease. Moreover, miR-338-5p decelerated apoptotic loss of neurons in APP/PS1 mice. MiR-338-5p decreased neuronal apoptosis in vitro induced by amyloid β accumulation, which was attributed to the negative regulation of BCL2L11 by miR-338-5p, since the restoration of BCL2L11 eliminated the protective role of miR-338-5p against neuronal apoptosis. Taken together, all of these results may indicate miR-338-5p as an innovative modulator in the pathogenesis of Alzheimer’s disease, and also suggest that the protective effect of miR-338-5p on neuronal apoptosis may underlie its beneficial effect on APP/PS1 mice.