CARBOXY-TERMINAL TRUNCATION OF LONG-TAILED AMYLOID BETA-PEPTIDE IS INHIBITED BY SERINE-PROTEASE INHIBITOR AND PEPTIDE ALDEHYDE

The 42/43-residue amyloid beta-peptide (A beta) 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 th ree amino acids from A beta 1-43. The carboxypeptidase activity in the brain was completely inhibited by 1 mM phenylmethylsulfonyl fluoride, suggesting the protease is a serine carboxypeptidase. The carboxy-ter minal truncation of A beta 1-43 was moderately inhibited by carbobenzo xy-Leu-leucinal, carbobenzoxy-Leu-Leu-leucinal, and carbobenzoxy-Leu-L eu-norvalinal, and weakly by antipain, The present data suggest that t he serine carboxypeptidase contributes to the generation of short-tail ed AP peptides and is important in the intracellular clearance of A be ta 1-42/43 in brains. (C) 1998 Federation of European Biochemical Soci eties.