Human apolipoprotein A-I natural variants: molecular mechanisms underlying amyloidogenic propensity

TRICERRI,M. A; ROSU, S. A; RAMELLA, N.A; GADDI, G; FINARELLI, G; SCHINELLA, G. R; PRIETO, E. D.

Uppsala

Simposio; The XVth International symposium on amyloidosis; 2016

International Society of Amyloidosis

Naturally occurring mutations of Human apolipoprotein A-I (apoA-I) have been shown to induce amyloidosis in patients, with a broad range of clinical manifestations, depending on the protein variant which is involved (1). Although the molecular mechanisms of apoA-I amyloid associated pathology remain largely unknown, the fact that the wild-type (Wt) deposits in atherosclerotic plaques supports the hypothesis that a chronic inflammatory micro environment could elicit protein aggregation (2). In order to get insight into the mechanisms inducing apoA-I misfolding, we examined the influence of the microenvironment on protein stability, aggregation propensity, as well as on the ability to bind to putative ligands and pathogenicity.