MicroRNA regulation of Alzheimer's Amyloid precursor protein expression
MicroRNA regulation of Alzheimer's Amyloid precursor protein expression
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DOI：
10.1016/j.nbd.2008.11.009
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发表时间：
2009-03-01
影响因子：
6.1
通讯作者：
De Strooper, Bart
中科院分区：
文献类型：
--
作者：
Hebert, Sebastien S.;Horre, Katrien;De Strooper, Bart
淀粉样前体蛋白（APP）基因剂量效应可导致家族性AD。最近的证据表明，参与基因转录控制的microRNA（miRNA）途径可能参与散发性阿尔茨海默病（AD）的发展。因此，我们研究了miRNAs是否可以参与APP基因表达的调节。我们发现，属于miR-20 a家族的miRNA（即miR-20 a，miR-17- 5 p和miR-106 b）可以在体外和神经元细胞系的内源性水平上调节APP的表达。在大脑发育和分化的神经元中发现这些miRNAs和APP之间的紧密相关性。因此，我们确定miRNA作为APP表达的新的内源性调节因子，这表明miRNA表达的变化可能有助于APP在发育和疾病过程中在大脑中表达的变化。在散发性AD患者中发现miR-106 b表达的统计学显著降低的观察结果进一步证实了这种可能性。(C)2008年爱思唯尔公司All rights reserved.
Gene dosage effects of Amyloid precursor protein (APP) can cause familial AD. Recent evidence suggest that microRNA (miRNA) pathways, implicated in gene transcriptional control, could be involved in the development of sporadic Alzheimer's disease (AD). We therefore investigated whether miRNAs could participate in the regulation of APP gene expression. We show that miRNAs belonging to the miR-20a family (that is, miR-20a, miR-17-5p and miR-106b) could regulate APP expression in vitro and at the endogenous level in neuronal cell lines. A tight correlation between these miRNAs and APP was found during brain development and in differentiating neurons. We thus identify miRNAs as novel endogenous regulators of APP expression, suggesting that variations in miRNA expression could contribute to changes in APP expression in the brain during development and disease. This possibility is further corroborated by the observation that a statistically significant decrease in miR-106b expression was found in sporadic AD patients. (C) 2008 Elsevier Inc. All rights reserved.