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MicroRNA-34c Downregulation Ameliorates Amyloid-β-Induced Synaptic Failure and Memory Deficits by Targeting VAMP2.
- Source :
- Journal of Alzheimer's Disease; 2015, Vol. 48 Issue 3, p673-686, 14p
- Publication Year :
- 2015
-
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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 13872877
- Volume :
- 48
- Issue :
- 3
- Database :
- Complementary Index
- Journal :
- Journal of Alzheimer's Disease
- Publication Type :
- Academic Journal
- Accession number :
- 110217155
- Full Text :
- https://doi.org/10.3233/JAD-150432