Department of Pharmacology, School of Basic Medical Sciences, Anhui Medical University, Hefei, Anhui, People's Republic of China.
The Second Clinical Medical School, Anhui Medical University, Hefei, Anhui, People's Republic of China.
J Parkinsons Dis. 2023;13(5):743-756. doi: 10.3233/JPD-225098.
Endophilin A1 (EPA1) is encoded by the SH3GL2 gene, and SH3GL2 was designated as a Parkinson's disease (PD) risk locus by genome-wide association analysis, suggesting that EPA1 may be involved in the occurrence and development of PD.
To investigate the role of EPA1 in lipopolysaccharide (LPS)-induced PD model mice.
The mice PD model was prepared by injecting LPS into the substantia nigra (SN), and the changes in the behavioral data of mice in each group were observed. The damage of dopaminergic neurons, activation of microglia, and reactive oxygen species (ROS) generation were detected by immunofluorescence method; calcium ion concentration was detected by calcium content detection kit; EPA1 and inflammation and its related indicators were detected by western blot method. EPA1 knockdown was performed by an adeno-associated virus vector containing EPA1-shRNA-eGFP infusion.
LPS-induced PD model mice developed behavioral dysfunction, SN dopaminergic nerve damage, significantly increased calcium ion, calpain 1, and ROS production, activated NLRP1 inflammasome and promoted pro-inflammatory cell release, and SN EPA1 knockdown improves behavioral disorders, alleviates dopaminergic neuron damage, reduces calcium, calpain 1, ROS generation, and blocks NLRP1 inflammasome-driven inflammatory responses.
The expression of EPA1 in the SN of LPS-induced PD model mice was increased, and it played a role in promoting the occurrence and development of PD. EPA1 knockdown inhibited the NLRP1 inflammasome activation, decreased the release of inflammatory factors and ROS generation, and alleviated dopaminergic neuron damage. This indicated that EPA1 may participating in the occurrence and development of PD.
内收蛋白 A1（EPA1）由 SH3GL2 基因编码，SH3GL2 通过全基因组关联分析被指定为帕金森病（PD）的风险基因座，提示 EPA1 可能参与 PD 的发生和发展。
探讨 EPA1 在脂多糖（LPS）诱导的 PD 模型小鼠中的作用。
通过向黑质（SN）注射 LPS 制备 PD 模型小鼠，观察各组小鼠的行为数据变化。采用免疫荧光法检测多巴胺能神经元损伤、小胶质细胞激活和活性氧（ROS）生成情况；采用钙含量检测试剂盒检测钙离子浓度；采用 Western blot 法检测 EPA1 及炎症及其相关指标。通过含有 EPA1-shRNA-eGFP 的腺相关病毒载体进行 EPA1 敲低。
LPS 诱导的 PD 模型小鼠出现行为功能障碍，SN 多巴胺能神经损伤，钙离子、钙蛋白酶 1 和 ROS 生成显著增加，NLRP1 炎性小体激活并促进促炎细胞释放，SN EPA1 敲低可改善行为障碍，减轻多巴胺能神经元损伤，减少钙离子、钙蛋白酶 1、ROS 生成，并阻断 NLRP1 炎性小体驱动的炎症反应。
LPS 诱导的 PD 模型小鼠 SN 中 EPA1 的表达增加，其在促进 PD 的发生和发展中发挥作用。EPA1 敲低抑制 NLRP1 炎性小体激活，减少炎症因子释放和 ROS 生成，减轻多巴胺能神经元损伤。这表明 EPA1 可能参与 PD 的发生和发展。
