Causal Effects of Microglia-Mediated Innate Immune Responses in the Pathogenesis of C9orf72 Frontotemporal Dementia and Amyotrophic Lateral Sclerosis.
PubMed(2021)
摘要
Microglia mediated neuroinflammation is present in FTD/ALS. In vivo, significant neuroinflammation was noted by increased microglia density and activation, with elevated IL-1β and active caspase-1. In vitro studies indicated a mechanism by which neurons can induce proliferation and activation of microglia in response to FTD/ALS neuropathologies. Genetic ablation of Nlrp3 resulted in significant attenuation of FTD/ALS neuropathologies, leading to improvements in behavior and survival. These data implicate microglia mediated innate immune responses as a potent target for treatment of FTD/ALS.
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