Glial cells in amyotrophic lateral sclerosis.
Glial cells in amyotrophic lateral sclerosis.
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DOI：
10.1155/2011/718987
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发表时间：
2011
影响因子：
1.5
通讯作者：
Yamanaka K
中科院分区：
文献类型：
--
作者：
Lasiene J;Yamanaka K
肌萎缩侧索硬化症（ALS）是一种以上下运动神经元过早死亡为特征的成人运动神经元疾病。2%的ALS病例是由超氧化物歧化酶1（SOD 1）基因的显性突变引起的，突变蛋白质的毒性增加。使用SOD1模型的遗传和嵌合小鼠研究表明，非神经元细胞通过非细胞自主机制在神经退行性变中发挥重要作用。我们从啮齿类动物模型和ALS患者的研究中综述了每种胶质细胞类型在ALS病理学中的贡献。星形胶质细胞增生和小胶质细胞增生不仅是该疾病的显著标志，而且小胶质细胞活化的强度与人ALS中运动神经元损伤的严重程度相关。受损的星形胶质细胞功能，如细胞外谷氨酸的清除和神经营养因子的释放与疾病有关。此外，星形胶质细胞和小胶质细胞内的损伤参与加速疾病进展。最后，其他神经胶质细胞，如NG2细胞，少突胶质细胞和雪旺细胞正在研究中，以确定它们在ALS中的作用。积累有关胶质细胞在疾病中的积极作用的知识应仔细应用于了解散发性ALS和开发针对胶质细胞的治疗方法。
Amyotrophic lateral sclerosis (ALS) is an adult motor neuron disease characterized by premature death of upper and lower motor neurons. Two percent of ALS cases are caused by the dominant mutations in the gene for superoxide dismutase 1 (SOD1) through a gain of toxic property of mutant protein. Genetic and chimeric mice studies using SOD1 models indicate that non-neuronal cells play important roles in neurodegeneration through non-cell autonomous mechanism. We review the contribution of each glial cell type in ALS pathology from studies of the rodent models and ALS patients. Astrogliosis and microgliosis are not only considerable hallmarks of the disease, but the intensity of microglial activation is correlated with severity of motor neuron damage in human ALS. The impaired astrocytic functions such as clearance of extracellular glutamate and release of neurotrophic factors are implicated in disease. Further, the damage within astrocytes and microglia is involved in accelerated disease progression. Finally, other glial cells such as NG2 cells, oligodendrocytes and Schwann cells are under the investigation to determine their contribution in ALS. Accumulating knowledge of active role of glial cells in the disease should be carefully applied to understanding of the sporadic ALS and development of therapy targeted for glial cells.