Apolipoprotein A-I induced amyloidosis

Amyloidosis is characterized by extracellular deposits of protein fibrils with a high content of beta-sheets in secondary structure, The protein forms together with proteoglycans amyloid fibrils causing organ damage and serious morbidity, Intact apolipoprotein A-I (apoA-I) is an important protein in lipid metabolism regulating the synthesis and catabolism of high density lipoproteins (HDL). Usually, apoA-I is not associated with amyloidosis. However, four naturally occuring mutant forms of apoA-I are known so far resulting in amyloidosis, The most important feature of all variants is the very similar formation of N-terminal fragments which mere found in the amyloid deposits (residues 1-83 to 1-94), The new insights in the understanding of the association of apoA-I with HDL, its metabolism, and its hypothesized structural findings may explain a common mechanism for the genesis of apoA-I induced amyloidosis, Here we summarized the specific features of all known amyloidogenic variants of apoA-I and speculate about its metabolic pathway, which may have general implications for the metabolism of apoA-I. (C) 1998 Federation of European Biochemical Societies.