MicroRNAs (miRNAs) are small (similar to 22-nucleotide [nt]) noncoding RNAs that regulate biological processes at the posttranscriptional level. Dysregulation of specific miRNAs leads to impaired synaptic plasticity resulting in Alzheimer's disease (AD). Amyloid-beta (A beta) accumulation is the most important pathogenic factor for AD development. Therefore, focusing on A beta-targeted miRNAs may have therapeutic implications for AD. We found that miR-34c, a miRNA that was previously reported to be upregulated in a transgenic AD model and patients, was significantly increased in hippocampal neurons exposed to A beta. Western blots and luciferase assay confirmed that increased miR-34c was closely related to VAMP2 reduction. Furthermore, miR-34c blockade upregulated VAMP2 expression and rescued synaptic failure as well as learning and memory deficits caused by A beta. The A beta-miR-34c-VAMP2 pathway mediates the sustained VAMP2 reduction in AD patients and provides a novel underlying epigenetic mechanism for attenuation of A beta toxicity in AD.
基金：
National Natural Science Foundation of China [81401047]
第一作者单位：[1]Huazhong Univ Sci & Technol,Dept Orthoped,Biol Engn & Regenerat Med Ctr,Tongji Hosp,TongJi Med Coll,Wuhan 430074,Peoples R China[2]Maternal & Childrens Hosp Hubei Prov, Dept Pathol, Wuhan, Peoples R China
通讯作者：
推荐引用方式(GB/T 7714)：
Hu Shunze,Wang Huan,Chen Kun,et al.MicroRNA-34c Downregulation Ameliorates Amyloid-β-Induced Synaptic Failure and Memory Deficits by Targeting VAMP2[J].JOURNAL OF ALZHEIMERS DISEASE.2015,48(3):673-686.doi:10.3233/JAD-150432.
APA：
Hu, Shunze,Wang, Huan,Chen, Kun,Cheng, Peng,Gao, Shutao...&Sun, Xuying.(2015).MicroRNA-34c Downregulation Ameliorates Amyloid-β-Induced Synaptic Failure and Memory Deficits by Targeting VAMP2.JOURNAL OF ALZHEIMERS DISEASE,48,(3)
MLA：
Hu, Shunze,et al."MicroRNA-34c Downregulation Ameliorates Amyloid-β-Induced Synaptic Failure and Memory Deficits by Targeting VAMP2".JOURNAL OF ALZHEIMERS DISEASE 48..3(2015):673-686
