Identification of molecules that correct structural and functional defects of naturally-occurring pathogenic apoA-I mutants

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Background and Aims : Naturally-occurring mutations in human apolipoprotein A-I (apoA-I) have been shown to disturb protein conformation and induce functional defects that impair the levels and atheroprotective properties of HDL. One such apoA-I mutation, L178P, induces major defects in the structural integrity and functions of the protein that may underlie the reduced HDL-cholesterol and increased cardiovascular risk observed in carriers of the mutation. Here, a library of marketed drugs (∼1000 compounds) was screened against apoA-I[L178P] to identify molecules that can prevent mutant apoA-I from adopting its pathological conformation.