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

FEBS Lett. 1998 Mar 13;424(3):136-8. doi: 10.1016/s0014-5793(98)00157-4.

Abstract

The 42/43-residue amyloid beta-peptide (Abeta) 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 Abeta1-43. 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 Abeta1-43 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 Abeta peptides and is important in the intracellular clearance of Abeta1-42/43 in brains.

MeSH terms

  • Amino Acids / metabolism
  • Amyloid beta-Peptides / chemistry
  • Amyloid beta-Peptides / drug effects
  • Amyloid beta-Peptides / metabolism*
  • Animals
  • Antipain / pharmacology*
  • Brain / enzymology
  • Carboxypeptidases / antagonists & inhibitors
  • Carboxypeptidases / metabolism
  • Chloromercuribenzoates / pharmacology
  • Edetic Acid / pharmacology
  • Leupeptins / pharmacology
  • Pepstatins / pharmacology
  • Peptide Fragments / chemistry
  • Peptide Fragments / drug effects
  • Peptide Fragments / metabolism*
  • Phenylmethylsulfonyl Fluoride / pharmacology
  • Rats
  • Serine Proteinase Inhibitors / pharmacology*
  • p-Chloromercuribenzoic Acid

Substances

  • Amino Acids
  • Amyloid beta-Peptides
  • Chloromercuribenzoates
  • Leupeptins
  • Pepstatins
  • Peptide Fragments
  • Serine Proteinase Inhibitors
  • amyloid beta-protein (1-43)
  • Streptomyces pepsin inhibitor
  • Antipain
  • Phenylmethylsulfonyl Fluoride
  • p-Chloromercuribenzoic Acid
  • Edetic Acid
  • Carboxypeptidases
  • leupeptin
  • pepstatin