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

FEBS Letters

Hamazaki, Hideaki¹ 

[1] Department of Biology, Kitasato University School of Medicine, Sagamihara, Kanagawa 228, Japan

关键词: Alzheimer's disease;    β-Amyloid;    Lysosomal carboxypeptidase;    Peptide aldehyde;    Proteasome inhibitor;    Calpain inhibitor;    Aβ;    amyloid β-peptide;    AD;    Alzheimer's disease;    APP;    β-amyloid precursor protein;    FAD;    familial Alzheimer's disease;    PMSF;    phenylmethylsulfonyl fluoride;    PCMB;    p-chloromercuribenzoic acid;    Z-;    carbobenzoxy-;    LeuH;    leucinal;    NvaH;    norvalinal;    AspH;    aspart-1-al;   

DOI  :  10.1016/S0014-5793(98)00157-4

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown