期刊
CELLS
卷 9, 期 6, 页码 -出版社
MDPI
DOI: 10.3390/cells9061442
关键词
neurodegeneration; unfolded protein response; BIP; IRE1 alpha; XBP1; miR-34a-5p; endoplasmic reticulum
类别
资金
- European Union's Seventh Framework Program for Research, Technological Development and Demonstration [600841]
- Michael J. Fox Foundation [14446]
Neurodegenerative disorders such as Alzheimer's disease (AD) and Parkinson's disease (PD) are characterized by the accumulation of misfolded proteins in the endoplasmic reticulum (ER) and the unfolded protein response (UPR). Modulating the UPR is one of the major challenges to counteract the development of neurodegenerative disorders and other diseases with affected UPR. Here, we show that miR-34a-5p directly targets the IRE1 alpha branch of the UPR, including the genesBIP,IRE1 alpha, andXBP1. Upon induction of ER stress in neuronal cells, miR-34a-5p overexpression impacts the resulting UPR via a significant reduction in IRE1 alpha and XBP1s that in turn leads to decreased viability, increased cytotoxicity and caspase activity. The possibility to modify the UPR signaling pathway by a single miRNA that targets central genes of the IRE1 alpha branch offers new perspectives for future therapeutic approaches against neurodegeneration.
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