脑卒中是我国高发病率、高死亡率的重大疾病，增加神经元存活是改善患者预后的关键，但现有神经保护剂疗效不理想，发现并鉴定新的神经保护剂迫在眉睫。.HSPA12A是主要表达于神经元的热休克蛋白。在前一项国家自然基金研究中我们发现，脑卒中后HSPA12A水平下降，而HSPA12A基因敲除加重脑卒中损伤、且该作用可能是通过抑制‘PINK1/Parkin/线粒体自噬’信号系统而加重神经元死亡介导的，提示HSPA12A高表达可能通过增加神经元存活而保护脑卒中。.本项目将在前期工作基础上，采用HSPA12A转基因鼠、基因敲除鼠，综合评价HSPA12A对脑卒中损伤的影响，并结合神经元培养模型，阐明“PINK1/Parkin”依赖的线粒体自噬在HSPA12A增加神经元存活中的作用，以明确HSPA12A保护脑卒中的机制。本研究将从增强线粒体质量控制的角度，为发现治疗脑卒中的新型神经保护剂提供前瞻性思路。

Stroke is a disastrous disease with high morbidity and mortality in China. Increase of neuronal survive is a promising approach for improving prognosis of stroke. However, the current clinically used neuroprotective agents are lack of high efficiency for neuroprotection against stroke. Discovering and characterizing novel neuroprotective agents is needed urgently. .HSPA12A is a heat shock protein that expressed predominantly in neurons. During our previous NSFC experiments, we observed that HSPA12A level is decreased dramatically following stroke. Moreover, HSPA12A knockout aggravates brain injury following stroke and this action could be mediated by increase of neuronal death through the inhibition of “PINK1/Parkin/mitophagy” axis. The data indicate that overexpression of HSPA12A could protect against stroke via improving neuronal survive. .Based on these pilot studies, we will evaluate the neuroprotection of HSPA12A against stroke using HSPA12A transgenic and knockout mice. Also, together with cell culture models, we will examine the role of “PINK1/Parkin/mitophagy” axis in the neuroprotection of HSPA12A against stroke. The results will provide evidence for discovering novel neuroprotective agents based on increasing mitochondrial quality control.