title: MicroRNA-146a represses LRP2 translation and leads to cell apoptosis in Alzheimer's disease.
abstract: MicroRNA regulation of transcript expression has been reported in patients with Alzheimer's disease (AD). Here, we investigate the role of microRNA-146a (miRNA-146a), a brain-enriched miRNA, which is upregulated in AD patients. Through analysis of predicted targets of miRNA-146a, low-density lipoprotein receptor-related protein-2 (Lrp2), a member of the LDLR family that is known to play a protective role in AD, was identified. Overexpression of miRNA-146a in SH-SY5Y cells significantly decreased Lrp2 expression, resulting in a reduction of Akt activation and induction of proapoptotic caspase-3, thereby increasing cell apoptosis. Thus, specific miRNA-146a regulation may contribute to AD by downregulating the Lrp2/Akt pathway.
authors.affiliation: Department of Neurology & Neuroscience Institute, Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, China.|Laboratory of Neurodegenerative Diseases, Institute of Health Science, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences and Shanghai Jiao Tong University School of Medicine, China.
authors.forename: Bei
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of Neurology & Neuroscience Institute, Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, China.
authors.forename: Li-Ling
authors.initials: LL
authors.lastname: Wang
authors.affiliation: Department of Neurology & Neuroscience Institute, Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, China.
authors.forename: Ru-Jing
authors.initials: RJ
authors.lastname: Ren
authors.affiliation: Department of Biochemistry and Center for Neurodegenerative Disease, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Eric B
authors.initials: EB
authors.lastname: Dammer
authors.affiliation: Research Laboratory of Cell Regulation, Shanghai Jiao Tong University School of Medicine, China.
authors.forename: Yong-Fang
authors.initials: YF
authors.lastname: Zhang
authors.affiliation: School of Medical Sciences, The University of New South Wales, Randwick, Australia.
authors.forename: Yue
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Neurology & Neuroscience Institute, Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, China.|Laboratory of Neurodegenerative Diseases, Institute of Health Science, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences and Shanghai Jiao Tong University School of Medicine, China.
authors.forename: Sheng-Di
authors.initials: SD
authors.lastname: Chen
authors.affiliation: Department of Neurology & Neuroscience Institute, Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Wang
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism*; D017209:Apoptosis; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D006801:Humans; D026561:Low Density Lipoprotein Receptor-Related Protein-2 / Q000096:biosynthesis* / Q000235:genetics; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D014176:Protein Biosynthesis; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D015854:Up-Regulation
chemical_list: C000597357:LRP2 protein, human; D026561:Low Density Lipoprotein Receptor-Related Protein-2; C542542:MIRN146 microRNA, human; D035683:MicroRNAs; D051057:Proto-Oncogene Proteins c-akt; C505407:CASP3 protein, human; D053148:Caspase 3
keywords: Alzheimer's disease; Lrp2; apoptosis; miRNA-146a