Affiliations: [a] Department of Orthopedics, Biological Engineering and Regenerative Medicine Center, Tongji Hospital, TongJi Medical College, HuaZhong University of Science and Technology, Wuhan, China | [b] Department of Pathology, Maternal and Children’s Hospital of Hubei Province, Wuhan, China
Correspondence:
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Correspondence to: Xuying Sun, Department of Orthopedics, Biological Engineering and Regenerative Medicine Center, Tongji Hospital, TongJi Medical College, HuaZhong University of Science and Technology, Wuhan, China. Tel./Fax: +86 27 83662497; [email protected]
Note: [1] These authors contributed equally to this work.
Abstract: MicroRNAs (miRNAs) are small (∼22-nucleotide [nt]) noncoding RNAs that regulate biological processes at the post-transcriptional level. Dysregulation of specific miRNAs leads to impaired synaptic plasticity resulting in Alzheimer’s disease (AD). Amyloid-β (Aβ) accumulation is the most important pathogenic factor for AD development. Therefore, focusing on Aβ-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 Aβ. 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 Aβ. The Aβ-miR-34c-VAMP2 pathway mediates the sustained VAMP2 reduction in AD patients and provides a novel underlying epigenetic mechanism for attenuation of Aβ toxicity in AD.
