Wu Qi, Ye Xiaoyang, Xiong Yi, Zhu Haili, Miao Jianting, Zhang Wei, Wan Jun
Shenzhen Key Laboratory for Neuronal Structural Biology, Biomedical Research Institute, Shenzhen Peking University - The Hong Kong University of Science and Technology Medical Center Shenzhen, China.
Department of Neurology, Tangdu Hospital, Fourth Military Medical University Xi'an City, China.
Front Mol Neurosci. 2016 Dec 8;9:140. doi: 10.3389/fnmol.2016.00140. eCollection 2016.
MicroRNAs are small non-coding RNAs that repress the expression of their target proteins. The roles of microRNAs in the development of Alzheimer's disease (AD) are not clear. In this study we show that miR-200c represses the expression of PTEN protein. PTEN downregulation by miR-200c supports the survival and differentiation of cultured neurons. AD is a progressive neurodegenerative disease signified by beta amyloid (Aβ) peptide aggregation and deposition. In a mouse model of AD that is induced by and Δ double transgenes, we found Aβ deposition results in neuronal ER stress that induces miR200c. Pharmacological blockade of ER stress inhibited Aβ-induced miR-200c overexpression in AD brains. MiR-200c was detected in the serum of both AD mice and human AD patients. These findings suggest that miR-200c functions as part of the neuronal cell-intrinsic adaptive machinery, and supports neuronal survival and differentiation in response to Aβ induced ER-stress by downregulating PTEN.
微小RNA是一类小的非编码RNA，可抑制其靶蛋白的表达。微小RNA在阿尔茨海默病（AD）发生发展中的作用尚不清楚。在本研究中，我们发现miR-200c可抑制PTEN蛋白的表达。miR-200c介导的PTEN下调可支持培养神经元的存活和分化。AD是一种进行性神经退行性疾病，其特征为β淀粉样蛋白（Aβ）肽聚集和沉积。在由 和Δ双转基因诱导的AD小鼠模型中，我们发现Aβ沉积导致神经元内质网应激，进而诱导miR-200c表达。内质网应激的药理学阻断可抑制AD脑内Aβ诱导的miR-200c过表达。在AD小鼠和人类AD患者的血清中均检测到miR-200c。这些发现表明，miR-200c作为神经元细胞内在适应性机制的一部分发挥作用，并通过下调PTEN来支持神经元在Aβ诱导的内质网应激反应中的存活和分化。
