Enhanced aggregation of beta-amyloid-containing peptides by extracellular matrix and their degradation by the 68 kDa serine protease prepared from human brain.
To explore whether extracellular matrix components in human brain affect the deposition and aggregation of beta-amyloid containing peptides, human brain samples from patients with sporadic Alzheimer's disease and normal aged were analyzed by Western blot analysis. All major beta-amyloid-containing peptides contained epitope(s) which is recognized by anti heparan sulfate antibody. Incubation of brain beta-amyloid-containing peptides with human collagen type IV in neutral pH efficiently generated a high molecular weight aggregated band, approximately 5-fold that of the control sample. We have previously found a serine protease which is capable of cleaving an oligopeptide at the N-terminus of beta-amyloid. In this study, the protease, which also contains heparan sulfate glycoconjugates, degraded the above brain peptides as natural substrates, although with different efficiency. These findings suggest that extra-cellular matrix components affect the processing and aggregation of beta-amyloid-containing peptides in human brain.
Matsumoto
A
A
Department of Radiation Biophysics and Genetics, Kobe University School of Medicine, Japan.
Enomoto
T
T
Fujiwara
Y
Y
Baba
H
H
Matsumoto
R
R
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D015153:Blotting, Western; D001921:Brain / Q000201:enzymology*; D000939:Epitopes; D005109:Extracellular Matrix / Q000378:metabolism*; D005260:Female; D006497:Heparan Sulfate / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D011233:Precipitin Tests; D012697:Serine Endopeptidases / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D000939:Epitopes; D006497:Heparan Sulfate; D012697:Serine Endopeptidases