可塑性相关蛋白5在癫痫疾病中通过抑制Bnip3L表达调节线粒体自噬参与惊厥的发生发展

癫痫是儿童常见的神经系统疾病，但目前癫痫的发生机制尚不清楚，我们课题组新的研究显示在惊厥中锌离子转运体1和磷脂酶A2的表达上调，提示惊厥中存在锌超载及其导致的质膜损伤和调节过程，锌超载和质膜损伤引起神经元细胞内氧化应激，使线粒体本身受到损伤。同时我们的预实验结果提示磷脂磷酸酶家族蛋白Plppr5具有主动参与调控惊厥的作用。因此我们推测Plppr5能够影响海马神经元惊厥后线粒体自噬水平，修复质膜损伤，发挥神经保护作用。本项目拟通过体内及体外实验系统研究验证：发育期惊厥海马Plppr5表达与神经元线粒体自噬性死亡有关，揭示Plppr5可以通过抑制Bnip3L影响线粒体自噬水平从而修复损伤的神经元质膜的病理机制及关键调控分子。籍此证明Plppr5是癫痫海马神经元质膜损伤，线粒体自噬，功能损伤修复的新靶点。

Epilepsy is a common neurological disease in children, while the mechanism of epilepsy is still unclear. A new study by our team showed that the expression of zinc ion transporter 1 and phospholipase A2 was up-regulated in seizure. It is suggested that zinc overload and plasma membrane damage and regulation process was relate to seizure. Zinc overload and plasma membrane damage cause intracellular oxidative stress, which damage the mitochondria. At the same time, our preliminary experimental results suggest that Plppr5 has an active role in regulating seizure. Therefore, we speculate that Plppr5 can influence mitophagy levels in hippocampus after seizure, so as to repair plasma membrane defect and exert neuroprotective effects. This project is planned to be verified by in vivo and in vitro experimental systems: Plppr5 expression in hippocampus during developmental seizure is related to mitophagy. To reveal that Plppr5 can affect the mitophagy level by inhibiting Bnip3L, thereby repairing the pathological mechanism and key regulatory molecules of plasma membrane defect. After the experiments we might propose a new point of view that Plppr5 is a new target for epilepsy hippocampal neuronal plasma membrane damage, mitochondrial autophagy and functional defect repair.