Mutant presenilin2 promotes apoptosis through the p53/miR-34a axis in neuronal cells.

Abstract

Neurodegenerative disorders have attracted attention in last decades due to their high incidence in the world. The p53/miR-34a axis triggers apoptosis and suppresses viability in multiple types of cells, but little is known about its role in neurodegenerative diseases. In this study, we showed that presenilin (PS)-2, a major gene associated with familial Alzheimer's disease (AD) could trigger the apoptosis through the p53/miR-34a axis in PC12 cells. First we found that PC12 cell viability was downregulated by PS-2 and mutant PS-2 overexpression, especially by mutant PS-2 overexpression. Then, we established a mutant PS-2-overexpressing PC12 cell line and confirmed that mutant PS-2 induced not only p53 but also miR-34a expression. The transfection of miR-34a inhibitor reversed PS-2-induced effects on cellular viability and apoptosis. Mutant PS-2 overexpression promoted caspase-3 expression, reduced Sirt1 and Bcl-2 expression, all of which were miR-34a downstream genes related with cell apoptosis. Moreover, mutant PS-2 also activated the p53/miR-34a axis and induced apoptosis in AD transgenic mice brain. These results implied that mutant PS-2 might promote the apoptosis of neuronal cells through triggering the p53/miR-34a axis. Altogether our results provide a novel insight into neurodegenerative disease and deepen our understandings of AD pathogenic processes.

• Authors: Liu-Hong Li, Qiu-Yun Tu, Xiao-Hua Deng, Jian Xia, De-Ren Hou, Ke Guo, Xiao-Hong Zi
• Journal: Brain research (Brain Res) Vol. 1662 Pg. 57-64 (05 01 2017) ISSN: 1872-6240 [Electronic] Netherlands
• PMID: 28189560 (Publication Type: Journal Article)
• Copyright: Copyright © 2017 Elsevier B.V. All rights reserved.

Chemical References

• MIRN34a microRNA, mouse
• MicroRNAs
• Presenilin-2
• Proto-Oncogene Proteins c-bcl-2
• Tumor Suppressor Protein p53
• Caspase 3
• Sirtuin 1

Topics

• Alzheimer Disease (etiology, genetics)
• Animals
• Apoptosis (genetics)
• Caspase 3 (metabolism)
• Genes, p53
• Mice
• Mice, Transgenic
• MicroRNAs (genetics, metabolism)
• Neurodegenerative Diseases (genetics)
• PC12 Cells
• Presenilin-2 (genetics, metabolism)
• Proto-Oncogene Proteins c-bcl-2 (metabolism)
• Rats
• Signal Transduction (drug effects)
• Sirtuin 1 (metabolism)
• Tumor Suppressor Protein p53 (metabolism)