Onset and progression in inherited ALS determined by motor neurons and microglia
Onset and progression in inherited ALS determined by motor neurons and microglia
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DOI：
10.1126/science.1123511
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发表时间：
2006-06-02
期刊：
影响因子：
56.9
通讯作者：
Cleveland, Don W.
中科院分区：
文献类型：
--
作者：
Boillee, Severine;Yamanaka, Koji;Cleveland, Don W.
超氧化物歧化酶的显性突变导致肌萎缩侧索硬化症（ALS），一种以运动神经元丧失为特征的进行性麻痹性疾病。使用携带可删除突变基因的小鼠，运动神经元内的表达被证明是疾病发作和疾病进展早期阶段的主要决定因素。减少小胶质细胞中的突变水平对早期疾病阶段几乎没有影响，但大大减缓了后期疾病的进展。因此，发作和进展代表了不同的疾病阶段，这些阶段由不同细胞类型内的突变作用定义，以产生运动神经元的非细胞自主杀伤;这些发现验证了靶向非神经元细胞的治疗，包括细胞替代。
Dominant mutations in superoxide dismutase cause amyotrophic lateral sclerosis (ALS), a progressive paralytic disease characterized by loss of motor neurons. With the use of mice carrying a deletable mutant gene, expression within motor neurons was shown to be a primary determinant of disease onset and of an early phase of disease progression. Diminishing the mutant levels in microglia had little effect on the early disease phase but sharply slowed later disease progression. Onset and progression thus represent distinct disease phases defined by mutant action within different cell types to generate non-cell-autonomous killing of motor neurons; these findings validate therapies, including cell replacement, targeted to the non-neuronal cells.