Salidroside protects SH-SY5Y from pathogenic α-synuclein by promoting cell autophagy via mediation of mTOR/p70S6K signaling
Salidroside protects SH-SY5Y from pathogenic α-synuclein by promoting cell autophagy via mediation of mTOR/p70S6K signaling
复制标题
红景天苷通过介导 mTOR/p70S6K 信号传导促进细胞自噬，保护 SH-SY5Y 免受致病性 α-突触核蛋白的侵害
DOI：
10.3892/mmr.2019.10285
复制
发表时间：
2019-07-01
影响因子：
3.4
通讯作者：
Yan, Jing
中科院分区：
文献类型：
--
作者：
Chen, Shasha;Cai, Feng;Yan, Jing
α-突触核蛋白（alpha-synuclein，alpha-syn）的异常聚集是帕金森病（Parkinson's disease，PD）的重要病理特征，对多巴胺能神经元具有细胞毒性，导致细胞损伤和凋亡。红景天苷（Salidroside，SAL）是中药红景天的主要活性成分。先前的研究表明，SAL对细胞衰老和神经变性具有细胞保护作用。然而，SAL在PD中的作用和作用机制仍不清楚。本研究使用α-syn的野生型和A53 T突变的过表达在SH-SY 5 Y细胞中诱导PD的神经元模型，其导致神经元毒性和降低的细胞增殖指数。SAL可剂量依赖性地增加PD模型组的细胞增殖指数。此外，SAL减轻了致病性磷酸化（Ser 129）α-syn表达以及微管相关蛋白1A/1B轻链3（LC 3）-I与LC 3-II表达的比例，这与自噬功能有关。此外，结果表明，SAL诱导的PD模型神经元保护的潜在机制可能涉及保护自噬，其主要通过mTOR/p70 S6 K减弱神经元中的α-syn的磷酸化，并且不依赖于PI 3 K/Akt信号通路。
The abnormal aggregation of alpha-synuclein (alpha-syn), which is an important pathological feature of Parkinson's disease (PD), is cytotoxic to dopaminergic neurons and causes cellular damage and apoptosis. Salidroside (SAL) is the main active component of the traditional Chinese medicine Rhodiola rosea. Previous research has demonstrated that SAL exerts cellular protection against cell senescence and neurodegeneration. However, the role and mechanism of action of SAL in PD remain unclear. The present study used overexpression of the wild-type and the A53T mutation of alpha-syn to induce a neuronal model of PD in SH-SY5Y cells, which led to neuronal toxicity and a reduced cell proliferation index. SAL increased the cell proliferation index of both PD model groups in a dose-dependent manner. Additionally, SAL alleviated pathogenic phosphorylated (Ser129) alpha-syn expression as well as the ratio of microtubule-associated proteins 1A/1B light chain 3 (LC3)-I to LC3-II expression, which is related to autophagic function. Furthermore, the results suggested that the underlying mechanism for the SAL-induced protection of PD model neurons may involve the preservation of autophagy, which attenuates the phosphorylation of alpha-syn in neurons predominantly via mTOR/p70S6K, and is independent of the PI3K/Akt signaling pathway.