Carboxy-terminal truncation of long-tailed amyloid β-peptide is inhibited by serine protease inhibitor and peptide aldehyde

Abstract

The 42/43-residue amyloid β-peptide (Aβ) is widely believed to play a major role in Alzheimer's disease. The present study shows that the rat brain contains a carboxypeptidase that efficiently deletes three amino acids from Aβ1–43. The carboxypeptidase activity in the brain was completely inhibited by 1 mM phenylmethylsulfonyl fluoride, suggesting the protease is a serine carboxypeptidase. The carboxy-terminal truncation of Aβ1–43 was moderately inhibited by carbobenzoxy-Leu-leucinal, carbobenzoxy-Leu-Leu-leucinal, and carbobenzoxy-Leu-Leu-norvalinal, and weakly by antipain. The present data suggest that the serine carboxypeptidase contributes to the generation of short-tailed Aβ peptides and is important in the intracellular clearance of Aβ1–42/43 in brains.