Exposing the effects of amyloidogenic variants on the maturation of HDL by the conformational analysis of apolipoprotein A-I

• Online Access: http://hdl.handle.net/2047/D20291521

Apolipoprotein A-I (apoA-I) is a key protein involved in the production of high-density lipoprotein (HDL) particles. Not only does apoA-I act as a structural scaffold for HDL, making up 70% of the protein composition, it acts as a mediator of protein-protein interactions, a receptor ligand, and an enzyme cofactor. HDL particles are involved in the cardioprotective reverse cholesterol transport (RCT) pathway, accordingly apoA-I has also been linked to cardiovascular health. Alternatively, in acquired amyloidosis apoA-I has the propensity to misfold and deposit as fibrils in arteries contributing to heart disease, the leading cause of death in both men and women. Approximately 20 naturally occurring mutations of apoA-I cause hereditary amyloidosis (AApoAI), a potentially fatal disease wherein N-terminal fragments of apoA-I deposit as plaques in various organs and damage them. A better understanding of the mechanism of apoA-I and AApoA-I misfolding is required for the development of novel therapeutic interventions.