期刊
FEBS LETTERS
卷 590, 期 14, 页码 2190-2200出版社
WILEY
DOI: 10.1002/1873-3468.12229
关键词
Alzheimer's disease; apoptosis; Lrp2; miRNA-146a
资金
- National Basic Research Development Program of China [2010CB945200, 2011CB504104]
- National Natural Science Foundation of China [81001426, 81171027, 81200842, 91332107]
- Shanghai Pujiang Program [15PJ1405400]
MicroRNA regulation of transcript expression has been reported in patients with Alzheimer's disease (AD). Here, we investigate the role of microRNA-146a (miRNA-146a), a brain-enriched miRNA, which is upregulated in AD patients. Through analysis of predicted targets of miRNA-146a, low-density lipoprotein receptor-related protein-2 (Lrp2), a member of the LDLR family that is known to play a protective role in AD, was identified. Overexpression of miRNA-146a in SH-SY5Y cells significantly decreased Lrp2 expression, resulting in a reduction of Akt activation and induction of proapoptotic caspase-3, thereby increasing cell apoptosis. Thus, specific miRNA-146a regulation may contribute to AD by downregulating the Lrp2/Akt pathway.
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