Leveraging knowledge of HDLs major protein ApoA1: Structure, function, mutations, and potential therapeutics.

Apolipoprotein A1 (ApoA1) is a member of the Apolipoprotein family of proteins. It's a vital protein that helps in the production of high-density lipoprotein (HDL) particles, which are crucial for reverse cholesterol transport (RCT). It also has anti-inflammatory, anti-atherogenic, anti-apoptotic, and anti-thrombotic properties. These functions interact to give HDL particles their cardioprotective characteristics. ApoA1 has recently been investigated for its potential role in atherosclerosis, diabetes, neurological diseases, cancer, and certain infectious diseases. Since ApoA1's discovery, numerous mutations have been reported that affect its structural integrity and alter its function. Hence these insights have led to the development of clinically relevant peptides and synthetic reconstituted HDL (rHDL) that mimics the function of ApoA1. As a result, this review has aimed to provide an organized explanation of our understanding of the ApoA1 protein structure and its role in various essential pathways. Furthermore, we have comprehensively reviewed the important ApoA1 mutations (24 mutations) that are reported to be involved in various diseases. Finally, we've focused on the therapeutic potentials of some of the beneficial mutations, small peptides, and synthetic rHDL that are currently being researched or developed, since these will aid in the development of novel therapeutics in the future. [Display omitted] • The main protein component of HDL is ApoA1 which prevents CVD and amyloidosis. • Mutations in ApoA1 polypeptide result in structural and functional changes. • Many mutations in ApoA1 increase the vulnerability to various diseases. • Some mutations of ApoA1 were reported to have a cardioprotective effect. • ApoA1 mimetic peptides raise HDL levels and enhance cardioprotection. [ABSTRACT FROM AUTHOR]