筋萎縮性側索硬化症におけるグリア病態・神経炎症

抄録

Neuroinflammation, characterized by activated astrocytes, microglia, infiltrating immune cells, and the subsequent production of inflammatory mediators, is a pathological process involved in the various neurodegenerative diseases including Amyotrophic lateral sclerosis (ALS). Moreover, increasing evidences suggest that activated glial cells and immune cells, the key players of neuroinflammation, contribute to disease progression of ALS by the non–cell autonomous mechanism. Activated microglia produce pro–inflammatory cytokines and other neurotoxic or neuroprotective molecules likely under a control by astrocytes and infiltrated T cells. In the peripheral blood of patients with ALS, immune balance showed to be relatively Th1–dominant with higher level of interferon–γ (IFN–γ). On the other hand, regulatory T cells (Tregs), the number of which is reduced in the peripheral blood of ALS patients, are thought to be important for neuroprotective inflammatory responses. Activated astrocytes exhibit upregulation of inflammatory genes in both familial and sporadic ALS and acquire neurotoxicities by reduction of glutamate uptake or production of unknown toxic factors. Astrocytes also have an important role in regulating neuroinflammation of ALS by interfering with the beneficial effects of neuroinflammation partly by production of transforming growth factor–β1. Many clinical trials for ALS targeting neuroinflammation, together with a further understanding of the role of neuroinflammation in disease, will lead to the development of novel therapeutics for ALS.