Brain and Nerve Research Centre, Concord Clinical School, The University of Sydney, Concord Hospital, Sydney, New South Wales, Australia.
Curr Opin Neurol. 2024 Oct 1;37(5):585-592. doi: 10.1097/WCO.0000000000001279. Epub 2024 May 22.
Neuroinflammation appears to be an important pathogenic process in amyotrophic lateral sclerosis (ALS). Dysfunction of central immune pathways, including activation of microglia and astrocytes, and peripherally derived immune cells, initiate noncell autonomous inflammatory mechanisms leading to degeneration. Cell autonomous pathways linked to ALS genetic mutations have been recently identified as contributing mechanism for neurodegeneration. The current review provides insights into the pathogenic importance of central and peripheral inflammatory processes in ALS pathogenesis and appraises their potential as therapeutic targets.
ALS is a multistep process mediated by a complex interaction of genetic, epigenetic, and environmental factors. Noncell autonomous inflammatory pathways contribute to neurodegeneration in ALS. Activation of microglia and astrocytes, along with central nervous system infiltration of peripherally derived pro-inflammatory innate (NK-cells/monocytes) and adaptive (cell-mediated/humoral) immune cells, are characteristic of ALS. Dysfunction of regulatory T-cells, elevation of pro-inflammatory cytokines and dysbiosis of gut microbiome towards a pro-inflammatory phenotype, have been reported as pathogenic mechanisms in ALS.
Dysregulation of adaptive and innate immunity is pathogenic in ALS, being associated with greater disease burden, more rapid disease course and reduced survival. Strategies aimed at modulating the pro-inflammatory immune components could be of therapeutic utility.
神经炎症似乎是肌萎缩侧索硬化症（ALS）的一个重要发病机制。中枢免疫途径的功能障碍，包括小胶质细胞和星形胶质细胞的激活以及外周来源的免疫细胞，启动非细胞自主炎症机制，导致神经变性。最近发现与 ALS 基因突变相关的细胞自主途径被认为是神经退行性变的一种机制。本综述深入探讨了中枢和外周炎症过程在 ALS 发病机制中的发病重要性，并评估了它们作为治疗靶点的潜力。
ALS 是一个多步骤的过程，由遗传、表观遗传和环境因素的复杂相互作用介导。非细胞自主炎症途径有助于 ALS 的神经变性。小胶质细胞和星形胶质细胞的激活，以及中枢神经系统中由外周衍生的促炎固有（NK 细胞/单核细胞）和适应性（细胞介导/体液）免疫细胞的浸润，是 ALS 的特征。调节性 T 细胞功能障碍、促炎细胞因子水平升高以及肠道微生物组向促炎表型的失调，已被报道为 ALS 的发病机制。
适应性和固有免疫的失调在 ALS 中是致病的，与更大的疾病负担、更快的疾病进程和降低的生存率相关。调节促炎免疫成分的策略可能具有治疗效用。
