Yan Wang, Chen Zhao-Ying, Chen Jia-Qi, Chen Hui-Min
Neurological Department of Internal Medicine, Ningbo No. 2 Hospital, Ningbo 315000, China.
Neurological Department of Internal Medicine, Ningbo No. 2 Hospital, Ningbo 315000, China.
Biochem Biophys Res Commun. 2018 Feb 19;496(4):1019-1024. doi: 10.1016/j.bbrc.2017.12.149. Epub 2017 Dec 27.
Long non-coding RNA nuclear paraspeckle assembly transcript 1 (lncRNA NEAT1) was found to be closely related to the pathological changes in brain and nervous system. However, the role of NEAT1 and its potential mechanism in Parkinson's disease (PD) largely remain uncharacterized.
In this study, PD mouse model was established by intraperitoneal injection of MPTP. The numbers of TH + neurons, NEAT1 expression and the level of PINK1, LC3-II, LC3-I protein were assessed in PD mice. SH-SY5Y cells were treated with MPP as PD cell model. RNA pull-down assay was used to identify the interaction between NEAT1 and PINK1 in vitro. The endogenous expression of NEAT1 was modified by lentiviral vector carrying interference sequence for NEAT1 in vivo.
The numbers of TH neurons significantly decreased in PD mice compared with the control. The expressions of NEAT1, PINK1 protein and LC3-II/LC3-I level were increased by MPTP in vitro and in vivo. Moreover, NEAT1 positively regulated the protein level of PINK1 through inhibition of PINK1 protein degradation. And NEAT1 mediated the effects of MPP on SH-SY5Y cells through stabilization of PINK1 protein. The results of in vivo experiments revealed that NEAT1 knockdown could effectively suppress MPTP-induced autophagy in vivo that alleviated dopaminergic neuronal injury.
LncRNA NEAT1 promoted the MPTP-induced autophagy in PD through stabilization of PINK1 protein.
长链非编码RNA核副斑点组装转录本1（lncRNA NEAT1）被发现与脑和神经系统的病理变化密切相关。然而，NEAT1在帕金森病（PD）中的作用及其潜在机制在很大程度上仍不清楚。
在本研究中，通过腹腔注射MPTP建立PD小鼠模型。评估PD小鼠中TH+神经元的数量、NEAT1表达以及PINK1、LC3-II、LC3-I蛋白的水平。用MPP处理SH-SY5Y细胞作为PD细胞模型。采用RNA下拉实验在体外鉴定NEAT1与PINK1之间的相互作用。在体内通过携带针对NEAT1干扰序列的慢病毒载体修饰NEAT1的内源性表达。
与对照组相比，PD小鼠中TH神经元的数量显著减少。MPTP在体外和体内均增加了NEAT1、PINK1蛋白的表达以及LC3-II/LC3-I水平。此外，NEAT1通过抑制PINK1蛋白降解正向调节PINK1蛋白水平。并且NEAT1通过稳定PINK1蛋白介导MPP对SH-SY5Y细胞的作用。体内实验结果表明，敲低NEAT1可有效抑制MPTP诱导的体内自噬，减轻多巴胺能神经元损伤。
lncRNA NEAT1通过稳定PINK1蛋白促进MPTP诱导的PD自噬。
