Role of Neuroinflammation in Amyotrophic Lateral Sclerosis: Cellular Mechanisms and Therapeutic Implications.

Role of Neuroinflammation in Amyotrophic Lateral Sclerosis: Cellular Mechanisms and Therapeutic Implications.
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神经炎症在肌萎缩侧索硬化症中的作用:细胞机制和治疗意义

DOI:
10.3389/fimmu.2017.01005
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发表时间:
2017
影响因子:
7.3
通讯作者:
Wang F
Wang F
中科院分区:
医学2区
文献类型:
--
作者:
Liu J;Wang F

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肌萎缩侧索硬化症(ALS)是一种进行性神经退行性疾病,其影响包括皮质脊髓束的上运动神经元(MN)和源自脑干核和脊髓腹根的下MN,导致致命性瘫痪。目前,还没有有效的治疗ALS的方法。越来越多的证据表明,神经炎症在ALS的发病机制中起着重要作用。ALS的神经炎症以淋巴细胞和巨噬细胞浸润、小胶质细胞和反应性星形胶质细胞活化以及补体参与为特征。在这篇综述中,我们重点讨论了ALS发病过程中神经炎症的关键细胞参与者,不仅讨论了它们的有害作用,而且还讨论了它们的免疫调节作用。我们将总结针对神经炎症的ALS的药理学疗法,以及旨在调节炎症环境以保留ALS患者和疾病动物模型中剩余MN的干细胞治疗领域的最新进展。
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that affects upper motor neurons (MNs) comprising the corticospinal tract and lower MNs arising from the brain stem nuclei and ventral roots of the spinal cord, leading to fatal paralysis. Currently, there are no effective therapies for ALS. Increasing evidence indicates that neuroinflammation plays an important role in ALS pathogenesis. The neuroinflammation in ALS is characterized by infiltration of lymphocytes and macrophages, activation of microglia and reactive astrocytes, as well as the involvement of complement. In this review, we focus on the key cellular players of neuroinflammation during the pathogenesis of ALS by discussing not only their detrimental roles but also their immunomodulatory actions. We will summarize the pharmacological therapies for ALS that target neuroinflammation, as well as recent advances in the field of stem cell therapy aimed at modulating the inflammatory environment to preserve the remaining MNs in ALS patients and animal models of the disease.
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