Soluble beta-amyloid peptides, but not insoluble fibrils, have specific effect on neuronal microRNA expression.
Soluble beta-amyloid peptides, but not insoluble fibrils, have specific effect on neuronal microRNA expression.
复制标题
DOI：
10.1371/journal.pone.0090770
复制
发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Liao FF
中科院分区：
文献类型：
--
作者：
Li JJ;Dolios G;Wang R;Liao FF
最近的研究表明，可溶性β-淀粉样蛋白（sAβ）低聚物，而不是它们的纤维聚集体，有助于阿尔茨海默病（AD）的发病机制，尽管它们的神经毒性机制仍然难以捉摸。在这里，我们证明来自7PA2细胞的sAβ对原代培养神经元中一组功能有效的microRNAs （miRNAs）的调节作用比合成的不溶性a β原纤维（fAβ）强得多。在我们的神经元模型中，更高浓度的合成sAβ肽对这些mirna有类似的作用。此外，sa β诱导的miR-134、miR-145和miR-210的表达被两种选择性n -甲基-d-天冬氨酸（NMDA）受体抑制剂完全逆转，但胰岛素和福斯克林都不能逆转，这表明这是一种NMDA受体依赖的调控机制，而不是PI3K/AKT或PKA/CREB信号依赖的调控机制。此外，含有7PA2 CM的sAβ对miR-107表达的抑制可能涉及多种机制和多种参与者，包括NMDA受体、n端截断的Aβ和活性氧（ROS）。
Recent studies indicate that soluble β-amyloid (sAβ) oligomers, rather than their fibrillar aggregates, contribute to the pathogenesis of Alzheimer's disease (AD), though the mechanisms of their neurotoxicity are still elusive. Here, we demonstrate that sAβ derived from 7PA2 cells exert a much stronger effect on the regulation of a set of functionally validated microRNAs (miRNAs) in primary cultured neurons than the synthetic insoluble Aβ fibrils (fAβ). Synthetic sAβ peptides at a higher concentration present comparable effect on these miRNAs in our neuronal model. Further, the sAβ-induced miR-134, miR-145 and miR-210 expressions are fully reversed by two selective N-methyl-d-aspartate (NMDA) receptor inhibitors, but are neither reversed by insulin nor by forskolin, suggesting an NMDA receptor-dependent, rather than PI3K/AKT or PKA/CREB signaling dependent regulatory mechanism. In addition, the repression of miR-107 expression by the sAβ containing 7PA2 CM is likely involved multiple mechanisms and multiple players including NMDA receptor, N-terminally truncated Aβ and reactive oxygen species (ROS).
登录
查看更多内容
影响因子：
5.6
作者：
Finnerty JR;Wang WX;Hébert SS;Wilfred BR;Mao G;Nelson PT
通讯作者：
Nelson PT
影响因子：
16.2
作者：
Edbauer, Dieter;Neilson, Joel R.;Foster, Kelly A.;Wang, Chi-Fong;Seeburg, Daniel P.;Batterton, Matthew N.;Tada, Tomoko;Dolan, Bridget M.;Sharp, Phillip A.;Sheng, Morgan
通讯作者：
Sheng, Morgan
DOI：
10.1523/jneurosci.1836-12.2012
发表时间：
2012-08-08
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Kwak YD;Wang B;Li JJ;Wang R;Deng Q;Diao S;Chen Y;Xu R;Masliah E;Xu H;Sung JJ;Liao FF
通讯作者：
Liao FF
影响因子：
5.3
作者：
Brouillette, Jonathan;Caillierez, Raphaelle;Buee, Luc
通讯作者：
Buee, Luc
DOI：
10.1073/pnas.0710263105
发表时间：
2008-04-29
影响因子：
11.1
作者：
Hebert, Sebastien S.;Horre, Katrien;De Strooper, Bart
通讯作者：
De Strooper, Bart