Inflammasome activation under high cholesterol load triggers a protective microglial phenotype while promoting neuronal pyroptosis.

ABSTRACT:

Background

Persistent inflammatory response in the brain can lead to tissue damage and neurodegeneration. In Alzheimer's disease (AD), there is an aberrant activation of inflammasomes, molecular platforms that drive inflammation through caspase-1-mediated proteolytic cleavage of proinflammatory cytokines and gasdermin D (GSDMD), the executor of pyroptosis. However, the mechanisms underlying the sustained activation of inflammasomes in AD are largely unknown. We have previously shown that high brain cholesterol levels promote amyloid-β (Aβ) accumulation and oxidative stress. Here, we investigate whether these cholesterol-mediated changes may regulate the inflammasome pathway.

Methods

SIM-A9 microglia and SH-SY5Y neuroblastoma cells were cholesterol-enriched using a water-solu

SUBMITTER: de Dios C 

PROVIDER: S-EPMC9996936 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature