A serine protease in Alzheimer's disease cells cleaves a 16K-peptide with flanking residues upstream to beta-amyloid-N-terminus as natural substrate.
A serine protease which cleaves an oligopeptide at the beta-amyloid (beta A4) N-terminus was identified and purified from extracellular fluid of familial Alzheimer's disease (FAD) lymphoblastoid cells. In order to search for a natural substrate that stands for a direct precursor of beta A4, C-terminal fragments of beta-amyloid precursor protein (APP) were prepared by immunoprecipitation of cytosol proteins with beta A4-specific antibody. The 16 kDa peptide with N-terminus 30 amino acids upstream from the beta A4-N-terminus, also existing in other hematopoietic cells, was proved to be a natural substrate for the protease in human lymphoid cells. Its cleaved fragment with beta A4-N-terminus was thought to be less amyloidogenic on the basis of its property of self-aggregation in acidic pH. The results suggest the significance of the unique cleavage site at beta A4-upstreams in generation and accumulation of beta A4.
Matsumoto
A
A
Department of Radiation Biophysics and Genetics, Kobe University School of Medicine, Japan.
Matsumoto
R
R
Baba
H
H
Fujiwara
Y
Y
D000544:Alzheimer Disease / Q000201:enzymology*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D015153:Blotting, Western; D003600:Cytosol / Q000378:metabolism; D006801:Humans; D008214:Lymphocytes / Q000201:enzymology; D010455:Peptides / Q000378:metabolism; D011233:Precipitin Tests; D012697:Serine Endopeptidases / Q000378:metabolism*; D013379:Substrate Specificity / Q000502:physiology
D016229:Amyloid beta-Peptides; D010455:Peptides; D012697:Serine Endopeptidases