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: Shunze Hu, Huan Wang, Kun Chen, Peng Cheng, Shutao Gao, Jian Liu, Xiao Li, Xuying Sun
• Journal: Journal of Alzheimer's disease : JAD (J Alzheimers Dis) Vol. 48 Issue 3 Pg. 673-86 ( 2015) ISSN: 1875-8908 [Electronic] Netherlands
• PMID: 26402112 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Amyloid beta-Peptides
• MIRN34 microRNA, human
• MIRN34 microRNA, rat
• MIRN34a microRNA, mouse
• MicroRNAs
• Peptide Fragments
• Vesicle-Associated Membrane Protein 2
• amyloid beta-protein (1-42)

Topics

• Amyloid beta-Peptides (metabolism)
• Animals
• Cell Line, Tumor
• Cell Survival (physiology)
• Down-Regulation
• HEK293 Cells
• Hippocampus (metabolism)
• Humans
• Maze Learning (physiology)
• Membrane Potentials (physiology)
• Memory Disorders (metabolism)
• Mice, Inbred C57BL
• MicroRNAs (metabolism)
• Peptide Fragments (metabolism)
• Rats, Sprague-Dawley
• Synapses (metabolism)
• Tissue Culture Techniques
• Vesicle-Associated Membrane Protein 2 (metabolism)