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Active roles of glial cells in neurodegenrative disease

机译:胶质细胞在神经退行性疾病中的积极作用

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Dominant mutations in the Cu/Zn superoxide dismutase (SOD1) gene lead to a familial form of amyotrophic lateral sclerosis (ALS). Although ubiquitous expression of mutant SOD1 provokes progressive, selective motor neuron degeneration in human and rodents due to an acquired toxic property (ies) of the mutant, the distinct roles of mutant toxicity within motor neurons and non-neuronal cells are recently established by our cell-type specific gene ablation from mutant SOD1 mice. The toxicity(ies) within astrocytes and microglia accelerates disease progression, indicating that glial cells contribute to non-cell autonomous neurodegeneration. Misregulated genes within glial cells that we isolated from symptomatic mutant SOD1 mice indicated the involvement of innate immune system. The inhibition of innate immune pathway in SOD1 mice significantly accelerated disease progression. These results indicate the active role of glial cells in modifying disease progression in ALS models.
机译:Cu / Zn超氧化物歧化酶(SOD1)基因中的主要突变导致家族性肌萎缩性侧索硬化症(ALS)。尽管由于突变体获得的毒性,突变体SOD1的普遍表达在人和啮齿动物中引起进行性,选择性运动神经元变性,但我们的细胞最近确定了突变体毒性在运动神经元和非神经元细胞中的独特作用突变型SOD1小鼠的B型特异性基因消融。星形胶质细胞和小胶质细胞内的毒性促进疾病进展,表明神经胶质细胞有助于非细胞自主神经变性。我们从有症状的突变型SOD1小鼠中分离出的神经胶质细胞内基因失调表明了先天免疫系统的参与。 SOD1小鼠先天免疫途径的抑制作用大大加快了疾病的发展。这些结果表明神经胶质细胞在改变ALS模型疾病进展中的积极作用。

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