Serum Amyloid A and AA Amyloidosis.

Amyloid-related diseases show marked extracellular deposition of nonbranching protein fibrils, called amyloid, in various soft organs. The mechanisms by which soluble amyloid precursor proteins transform into amyloid fibrils remain mainly obscure. Here we discuss data derived from alveolar hydatid cyst-infected (AHC) mouse model of inflammation-associated amyloid A (AA) amyloidosis and concepts related to the potential roles of oxidative stress-related factors and metabolism of monocytoid cell-associated serum amyloid A (SAA) precursor protein in AA fibril formation in vivo. Evidence shows that AA fibrils are generated intracellularly within the activated host monocytoid cells, which prior to and during AA fibril formation generate, among other oxidative stress-related derivatives, 4-hydroxynonenal, a lipid peroxidation product. We suggest that release of the AA fibrils formed intracellularly, either by exocytosis or cell death, could act as the "seed" for the nucleation-dependent expansion of extracellular AA fibril deposition. [ABSTRACT FROM AUTHOR]