The ASC inflammasome adapter governs SAA-derived protein aggregation in inflammatory amyloidosis

ABSTRACT: Extracellularly released molecular inflammasome assemblies (ASC specks) cross-seed Aβ amyloid in Alzheimer's disease. Here we show that ASC governs the extent of inflammation-induced amyloid A (AA) amyloidosis, a systemic disease caused by the aggregation and peripheral deposition of the acute-phase reactant serum amyloid A (SAA) in chronic inflammatory conditions. Using superresolution microscopy, we found that ASC colocalized tightly with SAA in human AA amyloidosis. Recombinant ASC specks accelerated SAA fibril formation and mass spectrometry after limited proteolysis showed that ASC interacts with SAA via its pyrin domain (PYD). In a murine model of inflammatory AA amyloidosis, splenic amyloid load was conspicuously decreased in Pycard-/- mice which lack ASC. Treatment with anti-ASC(PY

SUBMITTER: Marco Losa 

PROVIDER: S-SCDT-10_1038-S44321-024-00107-0 | biostudies-other |

REPOSITORIES: biostudies-other