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 super-resolution 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

SUBMITTER: Losa M 

PROVIDER: S-EPMC11393341 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature