机构：[a]Innovation Center for Neurological Disorders and Department of Neurology, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, Beijing, P.R. China神经科系统神经内科首都医科大学宣武医院[b]Beijing Key Laboratory of Geriatric Cognitive Disorders, Beijing, P.R. China[c]Clinical Center for Neurodegenerative Disease and Memory Impairment, Capital Medical University, Beijing, P.R. China[d]Center of Alzheimer’s Disease, Beijing Institute of Brain Disorders, Collaborative Innovation Center for Brain Disorders, Capital Medical University, Beijing, P.R. China[e]Key Laboratory of Neurodegenerative Diseases, Ministry of Education, Beijing, P.R. China
Imbalance between amyloid-β (Aβ) production and clearance results in Aβ accumulation. Regulating Aβ levels is still a hot point in the research of Alzheimer's disease (AD).To identify the differential expression of ATP-binding cassette A1 (ABCA1) and its upstream microRNA (miRNA) in AD models, and to explore their relationships with Aβ levels.Quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting were performed to determine the expression of ABCA1 in 5xFAD mice, SH-SY5Y cells treated with Aβ oligomers and SH-SY5YAβPP695 cells (AD models). TargetScan was used to predict the upstream miRNAs for ABCA1. Dual-luciferase assay was conducted to identify the regulation of the miRNA on ABCA1. qRT-PCR was used to measure the expression of miRNA in AD models. Finally, enzyme-linked immunosorbent assays were performed to detect Aβ 42 and Aβ40 levels.The expression of ABCA1 was significantly down regulated in AD models at both mRNA and protein levels. Dual-luciferase assay showed that miR-96-5p could regulate the expression of ABCA1 through binding to the 3 untranslated region of ABCA1. The level of miR-96-5p was significantly elevated in AD models. The expression of ABCA1 was enhanced while Aβ 42 levels and Aβ 42/Aβ 40 ratios were reduced in SH-SY5YAβPP695 cells after treated with miR-96-5p inhibitor.The current study found that miR-96-5p is the upstream miRNA for ABCA1. Suppression of miR-96-5p in AD models could reduce Aβ 42/Aβ 40 ratios via up regulating the expression of ABCA1, indicating that miR-96-5p plays an important role in regulating the content of Aβ.
基金：
This study was supported
by the Key Project of the National Natural Science
Foundation of China (81530036); the National Key
Scientific Instrument and Equipment Development
Project (31627803); the Key Project of the National
Natural Science Foundation of China (U20A20354);
Beijing Scholars Program; Beijing Brain Initiative
from Beijing Municipal Science & Technology Commission (Z201100005520016, Z20110000552
0017).
第一作者机构：[a]Innovation Center for Neurological Disorders and Department of Neurology, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, Beijing, P.R. China
通讯作者：
通讯机构：[a]Innovation Center for Neurological Disorders and Department of Neurology, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, Beijing, P.R. China[b]Beijing Key Laboratory of Geriatric Cognitive Disorders, Beijing, P.R. China[c]Clinical Center for Neurodegenerative Disease and Memory Impairment, Capital Medical University, Beijing, P.R. China[d]Center of Alzheimer’s Disease, Beijing Institute of Brain Disorders, Collaborative Innovation Center for Brain Disorders, Capital Medical University, Beijing, P.R. China[e]Key Laboratory of Neurodegenerative Diseases, Ministry of Education, Beijing, P.R. China[*1]Innovation Center for Neurological Disorders and Department of Neurology, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, 45 Changchun St., Beijing, 100053, China.[*2]Innovation Center for Neurological Disorders and Department of Neurology, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, 45 Changchun St., Beijing, 100053, China.
推荐引用方式(GB/T 7714)：
Min Zhu,Longfei Jia,Jianping Jia.Inhibition of miR-96-5p May Reduce Aβ 42/Aβ40 Ratio via Regulating ATP-Binding Cassette A1.[J].JOURNAL OF ALZHEIMERS DISEASE.2021,83(1):367-377.doi:10.3233/JAD-210411.
APA：
Min Zhu,Longfei Jia&Jianping Jia.(2021).Inhibition of miR-96-5p May Reduce Aβ 42/Aβ40 Ratio via Regulating ATP-Binding Cassette A1..JOURNAL OF ALZHEIMERS DISEASE,83,(1)
MLA：
Min Zhu,et al."Inhibition of miR-96-5p May Reduce Aβ 42/Aβ40 Ratio via Regulating ATP-Binding Cassette A1.".JOURNAL OF ALZHEIMERS DISEASE 83..1(2021):367-377
