MicroRNA-195 downregulates Alzheimer's disease amyloid-β production by targeting BACE1.
Alzheimer's disease (AD) is a progressive neurodegenerative disease, characterized by amyloid-beta (Aβ) deposition and neurofibrillary tangles. Numerous microRNAs have been found to play crucial roles in regulating Aβ 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 Aβ 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 Aβ, while inhibition of miR-195 resulted in an increase of Aβ. Thus, we demonstrated that miR-195 could downregulate the level of Aβ by inhibiting the translation of BACE1. We conclude that miR-195 might provide a therapeutic strategy for AD.
Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, PR China. zhuhongcan001@163.com
Hong-Can
HC
Zhu
Li-Mei
LM
Wang
Miao
M
Wang
Bo
B
Song
Song
S
Tan
Jun-Fang
JF
Teng
Dong-Xiao
DX
Duan
D020413:3' Untranslated Regions; D019588:Aging, Premature / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000544:Alzheimer Disease / Q000628:therapy; D053829:Amyloid Precursor Protein Secretases / Q000235:genetics* / Q000502:physiology; D016229:Amyloid beta-Peptides / Q000096:biosynthesis*; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000235:genetics* / Q000502:physiology; D001665:Binding Sites; D045744:Cell Line, Tumor; D015536:Down-Regulation; D057809:HEK293 Cells; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D006801:Humans; D051379:Mice; D008818:Mice, Neurologic Mutants; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D016297:Mutagenesis, Site-Directed; D009447:Neuroblastoma / Q000473:pathology; D014176:Protein Biosynthesis; D025941:Protein Interaction Mapping; D011499:Protein Processing, Post-Translational; D020871:RNA Stability; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000502:physiology
D020413:3' Untranslated Regions; D016229:Amyloid beta-Peptides; C552722:MIRN195 microRNA, human; C569389:MIRN195a microRNA, mouse; D035683:MicroRNAs; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human; C509282:Bace1 protein, mouse