α- 突触核蛋白对小鼠星形胶质细胞的激活作用

Alpha synuclein activates astrocytes in mice

摘要:

目的 研究外源性α- 突触核蛋白（α-syn）及其A53T 突变型对星形胶质细胞的激活作 用。方法 分离培养小鼠原代星形胶质细胞，经α-syn 和A53T 刺激后，用实时荧光定量聚合酶链反应和 Western blot 检测Toll 样受体（TLRs）和核转录因子-κB（NF-κB）的表达变化。结果 与对照组比较，2 种α-syn 提高TLRs1 ～ 4 和NF-κB 的表达水平（P <0.05），其中A53T 作用更强；Western blot 检测结果 表明，A53T 提高TLR2 和NF-κB 的蛋白水平。结论 α-syn 激活星形胶质细胞介导的固有免疫反应，为 神经退行性疾病机制提供免疫学证据。

Abstract:

Objective To investigate the activation effect of α-synuclein (α-syn) on astrocytes and innate immunity. Methods Primary astrocytes of mice were isolated and treated with α-syn (wild type, Wt) and its A53T mutant. Quantitative real-time PCR (qRT-PCR) and Western blot analysis were used to examine altered expressions of toll-like receptors (TLRs) 1-4 and NF-κB. Results In comparison with the control groups, Wt α-syn and its A53T mutant increased mRNA expressions of TLRs 1-4 and NF-κB, displaying a statistical significance (P < 0.05), with the A53T mutant having more potent immune induction effect than Wt α-syn. Western blot analysis showed the A53T mutant upregulated protein expressions of TLR2 and NF-κB. Conclusions Alpha synuclein is a powerful immunogenic substance to activate the astrocyte-mediated innate immune response, which provides a strong immunological evidence for the pathogenesis of neurodegenerative diseases.