title: MicroRNA-29c targets β-site amyloid precursor protein-cleaving enzyme 1 and has a neuroprotective role in vitro and in vivo.
abstract: Alzheimer's disease (AD), characterized by β-amyloid deposition and neurodegeneration, is the most common cause of dementia worldwide. Emerging evidence suggests that ectopic expression of micro (mi)RNAs is involved in the pathogenesis of AD. There is increasing evidence that miRNAs expressed in the brain are involved in neuronal development, survival and apoptosis. The expression of β-site amyloid precursor protein-cleaving enzyme 1 (BACE1) is regulated by dysregulated miRNAs in the brain. The present study determined the expression levels of the miRNA-29 (miR-29) family in peripheral blood samples of patients with AD and demonstrated a marked decrease in the expression of miR-29c compared with age-matched controls. In addition, a significant increase in the expression of BACE1 was observed in the peripheral blood of patients with AD. Correlation analysis revealed that the expression of miR-29c was negatively correlated with the protein expression of BACE1 in the peripheral blood samples from patients with AD. The present study also investigated the role of miR-29 on hippocampal neurons in vitro and in vivo. The results demonstrated that the upregulation of miR-29c promoted learning and memory behaviors in SAMP8 mice, at least partially, by increasing the activity of protein kinase A/cAMP response element-binding protein, involved in neuroprotection. This evidence suggested that miR-29c may be a promising potential therapeutic target against AD.
authors.affiliation: Department of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.
authors.forename: Guoshuai
authors.initials: G
authors.lastname: Yang
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Yanmin
authors.initials: Y
authors.lastname: Song
authors.affiliation: Department of Neurology, Haikou People's Hospital, Haikou, Hainan 570208, P.R. China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Department of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.
authors.forename: Yidong
authors.initials: Y
authors.lastname: Deng
authors.affiliation: Department of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.
authors.forename: Tao
authors.initials: T
authors.lastname: Liu
authors.affiliation: Department of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.
authors.forename: Guohu
authors.initials: G
authors.lastname: Weng
authors.affiliation: Department of Neurology, Haikou People's Hospital, Haikou, Hainan 570208, P.R. China.
authors.forename: Dan
authors.initials: D
authors.lastname: Yu
authors.affiliation: Department of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.
authors.forename: Suyue
authors.initials: S
authors.lastname: Pan
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D053829:Amyloid Precursor Protein Secretases / Q000235:genetics* / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000235:genetics* / Q000378:metabolism; D050882:CREB-Binding Protein / Q000235:genetics / Q000378:metabolism; D016022:Case-Control Studies; D049109:Cell Proliferation; D017868:Cyclic AMP-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008297:Male; D018782:Maze Learning; D051379:Mice; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D061251:Primary Cell Culture; D015398:Signal Transduction
chemical_list: D016229:Amyloid beta-Peptides; C532045:MIRN29a microRNA, human; D035683:MicroRNAs; D050882:CREB-Binding Protein; C494364:Crebbp protein, mouse; D017868:Cyclic AMP-Dependent Protein Kinases; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human