A RIPK1-regulated inflammatory microglial state in amyotrophic lateral sclerosis

作者：Lauren Mifflin, Zhirui Hu, Connor Dufort, Cynthia C. Hession, Alec J. Walker, Kongyan Niu, Hong Zhu, Nan Liu, Jun S. Liu, Joshua Z. Levin, Beth Stevens, Junying Yuan, Chengyu Zou · 发表于：Proceedings of the National Academy of Sciences · 年份：2021 · DOI：10.1073/pnas.2025102118 · 被引用次数：71 · 研究领域：Neuroinflammation and Neurodegeneration Mechanisms、Amyotrophic Lateral Sclerosis Research、Nerve injury and regeneration

Significance Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease. Inhibition of RIPK1, a kinase which regulates cell death and neuroinflammation, has been efficacious in treating mouse models of ALS. RIPK1 inhibitors have reached phase 2 clinical trials in ALS patients. Here, we explore the impact of RIPK1 inhibition on microglial-mediated neuroinflammation in ALS mouse models. We find that there is a subclass of microglia which produces proinflammatory cytokines in a RIPK1-dependent manner, and that this population is reduced by RIPK1 inhibition. We believe that these inflammatory microglia are a hallmark of ALS which may be clinically relevant in advancing RIPK1 inhibitors as a potential ALS therapy.