Immune-mediated mechanisms in the pathoprogression of amyotrophic lateral sclerosis.

Immune-mediated mechanisms in the pathoprogression of amyotrophic lateral sclerosis.
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DOI:
10.1007/s11481-013-9489-x
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发表时间:
2013-09
影响因子:
6.2
通讯作者:
Appel, Stanley H.
Appel, Stanley H.
中科院分区:
医学3区
文献类型:
--
作者:
Zhao, Weihua;Beers, David R.;Appel, Stanley H.

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肌萎缩性侧索硬化症(ALS)是一种毁灭性的神经退行性疾病,具有选择性地丧失上、下运动神经元。在运动神经元损伤部位,神经炎症是一个突出的病理发现,其特征是小胶质细胞活化、星形胶质增生、单核细胞和t细胞浸润。在动物模型和ALS患者中,先天免疫和适应性免疫反应都积极影响疾病进展,并在疾病的不同阶段促进神经保护或神经毒性。早期免疫系统对受损运动神经元信号的反应是挽救和修复受损组织。随着疾病的加速,从有益的免疫反应(涉及M2小胶质细胞和调节性t细胞)转变为有害的免疫反应(涉及M1小胶质细胞和Th1细胞)。在这篇综述中,我们强调了免疫介导机制在ALS发病机制中的重要性,并讨论了免疫细胞在疾病不同阶段的改变和不同的表型。我们越了解免疫系统在疾病过程中发生的动态变化,我们就越能开发出有效的治疗方案。
Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease with selective loss of upper and lower motor neurons. At sites of motor neuron injury, neuroinflammation is a prominent pathological finding and is characterized by microglial activation, astrogliosis, and infiltration of monocytes and T-cells. Both innate and adaptive immune responses actively influence disease progression in animal models and in ALS patients, and promote neuroprotection or neurotoxicity at different stages of disease. The early immune reaction to signals from injured motor neurons is to rescue and repair damaged tissue. As disease accelerates, a shift occurs from beneficial immune responses (involving M2 microglia and regulatory T-cells) to deleterious immune responses (involving M1 microglia and Th1 cells). In this review, we underscore the importance of immune-mediated mechanisms in the pathogenesis of ALS and discuss the alterations and distinct phenotypes of immune cells at the different stages of disease. The better we understand the dynamic changes that occur within the immune system over the course of disease, the better we will be able to develop effective therapeutic regimens in ALS.
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通讯作者: Appel, Stanley H.