肌萎缩侧索硬化症( amyotrophic lateral sclerosis，ALS) 是一种以选择性侵犯脑与脊髓的上、下运动神经元的神经系统变性疾病。内质网应激（ER stress) 是由于多种应激源引起的，导致蛋白错误折叠和未折叠蛋白聚集，细胞为恢复内质网功能而进行的一系列调节反应。研究表明ER stress与ALS密切相关，通过降低或者抑制ER stress能缓解ALS小鼠的疾病进程。我们前期研究表明EMC3（ER membrane protein complex subunit 3）能抵抗ER stress，并且初步研究表明在ALS小鼠中枢神经系统中过表达EMC3，可延长ALS小鼠的生存期。我们提出假说：在中枢神经系统中过表达EMC3，能够缓解内质网应激，保护运动神经元，延缓ALS发病。本项目将有助于深入理解ER stress在ALS发病过程中的调控作用，为ALS治疗提供靶点。

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that selectively affects the upper and lower motor neurons of the brain and spinal cord.ER stress is caused by a variety of stressors, resulting in protein misfolding and unfoldable protein aggregation,and a series of regulatory responses by cells to restore ER function. Studies have shown that ER stress is closely related to ALS,and can alleviate the disease process in mice with ALS by reducing or inhibiting ER stress.Our previous studies have shown that EMC3 (ER membrane protein complex subunit 3) can resist ER stress, and preliminary studies have shown that overexpression of EMC3 in the central nervous system of ALS mice can prolong the survival of ALS mice.We hypothesized that the overexpression of EMC3 in the central nervous system can relieve ER stress, protect motor neurons, and delay the onset of ALS.This project will help to understand the regulatory role of ER stress in the pathogenesis of ALS and provide a target for the treatment of ALS.