Carbamylation of the amino‐terminal residue (Gly1) of mouse serum amyloid A promotes amyloid formation in a cell culture model

Abstract

Amyloid A (AA) amyloidosis is a fatal protein deposition disease afflicting a small percentage of patients with chronic inflammation. Factors other than inflammation that determine development of AA amyloidosis remain largely unknown. The subunit protein comprising AA amyloid fibrils is derived from serum amyloid A (SAA), specifically its amino-terminal portion. In this in vitro study, carbamylation of residues in this region (primarily Gly1 but also Lys24) was shown to markedly increase amyloid-forming propensity as judged by extensive accumulation of amyloid in cell cultures. Contrastingly, no amyloid deposition occurred in cultures given SAA having a noncarbamylated amino terminus. Carbamylation, known to occur during uremia or inflammation, merits investigation as a potential determinant of AA amyloid fibril formation.

Dietary Intake of Rosmarinic Acid Increases Serum Inhibitory Activity in Amyloid A Aggregation and Suppresses Deposition in the Organs of Mice

“…Amyloidosis, which is characterized by the extracellular deposition of β-sheet-rich amyloid fibrils, is currently classified into more than 30 different types of medical associations based on precursor proteins or peptides [ 1 , 2 , 3 ]. Amyloid A (AA) amyloidosis is a protein-based disease frequently found in humans and livestock around the world [ 4 , 5 , 6 ].…”