Conformation of human apolipoprotein A-I amyloid variants: folding and the role of inflammation in the protein aggregation disease

TRICERRI, MA; GISONNO, R; RAMELLA; NA; ROSU; SA; JUAN P GORGOJO; GADDI; GM; PRIETO; ED; CORTEZ, MF; SCHINELLA, G; CURTO, ML; M EUGENIA RODRIGUEZ; FINARELLI; GS

TARRAGONA

Simposio; XVII International Symposium on Amyloidosis,; 2020

ISA

The reasons that determine the pathological deposition of human apolipoprotein A-I variantsinducing organ failure have been under research since the early description of natural mutationsin patients. Different protein conformations may be involved in the development of clinicalmanifestations associated with human amyloidosis. Although a fibrillar conformation is usually thesignature of damage in the tissues, it is not clear whether this species is per se the cause or theconsequence of the disease. From the more than 20 amyloidogenic variants of apoA-I described(Figure 1), a mutation leading to a deletion at position 107 (Lys107-0) has a unique pattern, aspatients carrying this variant show amyloidosis and severe atherosclerosis. Here we intended tocharacterize protein aggregation structures, and to test the hypothesis that a pro-inflammatorymicroenvironment could favor protein misfolding.