RIPK1 mediates a disease-associated microglial response in Alzheimer’s disease

2017/09/13 by Dimitry Ofengeim, Sonia Mazzitelli, Yasushi Ito +10 · 32 citations
Neuroscience · Medicine · Immunology and Microbiology · #Neuroinflammation and Neurodegeneration Mechanisms #Alzheimer's disease research and treatments #Atherosclerosis and Cardiovascular Diseases

paper · doi:10.1073/pnas.1714175114

Abstract

, a marker for disease-associated microglia (DAM), which encodes an endosomal/lysosomal cathepsin inhibitor named Cystatin F. We present evidence that RIPK1-mediated induction of Cst7 leads to an impairment in the lysosomal pathway. These data suggest that RIPK1 may mediate a critical checkpoint in the transition to the DAM state. Together, our study highlights a non-cell death mechanism by which the activation of RIPK1 mediates the induction of a DAM phenotype, including an inflammatory response and a reduction in phagocytic activity, and connects RIPK1-mediated transcription in microglia to the etiology of AD. Our results support that RIPK1 is an important therapeutic target for the treatment of AD.

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