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 occurring 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 were 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.
Abteilung Gastroenterologie und Hepatologie, Medizinische Hochschule Hannover, Germany.
J
J
Genschel
R
R
Haas
M J
MJ
Pröpsting
H H
HH
Schmidt
D000686:Amyloidosis / Q000378:metabolism*; D016632:Apolipoprotein A-I / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D014644:Genetic Variation; D006801:Humans; D017433:Protein Structure, Secondary
D016632:Apolipoprotein A-I