title: MicroRNA-34c Downregulation Ameliorates Amyloid-β-Induced Synaptic Failure and Memory Deficits by Targeting VAMP2.
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.
authors.affiliation: Department of Orthopedics, Biological Engineering and Regenerative Medicine Center, Tongji Hospital, TongJi Medical College, HuaZhong University of Science and Technology, Wuhan, China.|Department of Pathology, Maternal and Children's Hospital of Hubei Province, Wuhan, China.
authors.forename: Shunze
authors.initials: S
authors.lastname: Hu
authors.affiliation: Department of Orthopedics, Biological Engineering and Regenerative Medicine Center, Tongji Hospital, TongJi Medical College, HuaZhong University of Science and Technology, Wuhan, China.
authors.forename: Huan
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Orthopedics, Biological Engineering and Regenerative Medicine Center, Tongji Hospital, TongJi Medical College, HuaZhong University of Science and Technology, Wuhan, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Chen
authors.affiliation: Department of Orthopedics, Biological Engineering and Regenerative Medicine Center, Tongji Hospital, TongJi Medical College, HuaZhong University of Science and Technology, Wuhan, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Cheng
authors.affiliation: Department of Orthopedics, Biological Engineering and Regenerative Medicine Center, Tongji Hospital, TongJi Medical College, HuaZhong University of Science and Technology, Wuhan, China.
authors.forename: Shutao
authors.initials: S
authors.lastname: Gao
authors.affiliation: Department of Orthopedics, Biological Engineering and Regenerative Medicine Center, Tongji Hospital, TongJi Medical College, HuaZhong University of Science and Technology, Wuhan, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Orthopedics, Biological Engineering and Regenerative Medicine Center, Tongji Hospital, TongJi Medical College, HuaZhong University of Science and Technology, Wuhan, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Orthopedics, Biological Engineering and Regenerative Medicine Center, Tongji Hospital, TongJi Medical College, HuaZhong University of Science and Technology, Wuhan, China.
authors.forename: Xuying
authors.initials: X
authors.lastname: Sun
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000502:physiology; D015536:Down-Regulation; D057809:HEK293 Cells; D006624:Hippocampus / Q000378:metabolism; D006801:Humans; D018782:Maze Learning / Q000502:physiology; D008564:Membrane Potentials / Q000502:physiology; D008569:Memory Disorders / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D013569:Synapses / Q000378:metabolism; D046509:Tissue Culture Techniques; D050988:Vesicle-Associated Membrane Protein 2 / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; C522425:MIRN34 microRNA, human; C560944:MIRN34 microRNA, rat; C551848:MIRN34a microRNA, mouse; D035683:MicroRNAs; D010446:Peptide Fragments; D050988:Vesicle-Associated Membrane Protein 2; C075222:amyloid beta-protein (1-42)
keywords: Alzheimer’s disease; VAMP2; amyloid-β; miR-34c