肌萎缩脊髓侧索硬化症（ALS）是以运动神经元进行性变性、肌萎缩为主要特征的神经退行性疾病。目前，ALS的病因及发病机制仍不明确，尚无有效的治疗方法。作为局部微环境主要构成的星形胶质细胞是否在ALS运动神经元选择性、进行性退变中发挥主导作用尚不清楚。我们前期研究发现，神经退行性病变激活了Wnt/β-catenin信号通路，促进了星形胶质细胞的增生，与ALS发病密切相关。本课题拟用SOD1G93A ALS转基因鼠以及SOD1G93A突变的星形胶质细胞和运动神经元共培养细胞模型，系统研究ALS发生发展中神经元-胶质细胞之间的相互作用，从新的角度揭示星形胶质细胞在ALS运动神经元选择性、进行性变性中的作用；阐明Wnt信号通路调控星形胶质细胞对运动神经元的作用；并通过基因修饰的胶质前体细胞移植等干预手段，观察移植细胞对运动神经元的保护作用，寻找有效治疗ALS的新靶点，为ALS临床治疗提供理论依据。

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the progressive and fatal loss of motor neurons and muscular atrophy. The etiology and exact mechanisms of ALS are as yet undefined and few therapeutic options have emerged for slowing down disease progression. Astrocytes are one of the main cells composing the local microenvironment. It is still unclear whether or not astrocytes are responsible for motor neuron degeneration in ALS. Our previous study showed that neurodegeneration activated the Wnt/β-catenin signaling pathway and promoted the proliferation of astrocytes,which is involved in the pathogenesis of ALS in adult transgenic mice. In this study, we seek to examine the relationship between astrocytes and motor neuron degeneration using SOD1G93A transgenic ALS mice and cell models from coculture of motor neuron and astrocytes with mutation SOD1, so as to reveal the role of astrocytes in progressive loss of motor neurons of ALS from a new angle. We will elucidate the role of Wnt signaling pathway for motor neuron by regulating the astrocytes.Using the interventions of gene modified glial precursor cell transplantation,we will observe the protective roles of the transplanted cells to motor neuron in order to find new effective targets in treating ALS, thereby offerring sound theoretical basis for clinical treatment of ALS.