期刊
BRAIN RESEARCH BULLETIN
卷 88, 期 6, 页码 596-601出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.brainresbull.2012.05.018
关键词
Alzheimer's disease; microRNA; miR-195; BACE1
Alzheimer's disease (AD) is a progressive neurodegenerative disease, characterized by amyloid-beta (A beta) deposition and neurofibrillary tangles. Numerous microRNAs have been found to play crucial roles in regulating A beta production in the process of AD. Previous investigations have reported lower levels of many microRNAs in AD patients and animal models. Here, we examined the role of miR-195 in the process of A beta formation. Bioinformatics' algorithms predicted miR-195 binding sites within the beta-site APP cleaving enzyme 1 (BACE1)3'-untranslated region (3'-UTR), and we found the level of miR-195 to be negatively related to the protein level of BACE1 in SAMP8 mice. We confirmed the target site in HEK293 cells by luciferase assay. Overexpression of miR-195 in N2a/WT cells decreased the BACE1 protein level, and inhibition of miR-195 resulted in increase of BACE1 protein level. Furthermore, overexpression of miR-195 in N2a/APP decreased the level of A beta, while inhibition of miR-195 resulted in an increase of A beta. Thus, we demonstrated that miR-195 could downregulate the level of A beta by inhibiting the translation of BACE1. We conclude that miR-195 might provide a therapeutic strategy for AD. (C) 2012 Elsevier Inc. All rights reserved.
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