Characterization of proteases with the specificity to cleave at the secretase-site of beta-APP.
The beta-amyloid precursor protein (APP) can be proteolytically processed in at least two different ways either in a secretory pathway or in a lysosomal pathway. The proposed sites for the 'secretase' cleavage are the Gln15-Lys16 and Lys16-Leu17 peptide bonds within the beta A4 domain. Using chromogenic peptide substrates derived from these APP sites, proteolytic enzymes were investigated in the brain of AD patients and control individuals. Mean differences in enzyme activity were observed between the two groups, although no statistical significance was reached. Further analysis in rat brain allowed identification of the lysosomal cathepsin B and the cytosolic proteasome as secretase-like enzymes. They are probably not involved in APP secretion but possibly in removal of amyloidogenic fragments.
Schönlein
C
C
Pharma Division, F. Hoffmann-La Roche Ltd., Basel, Switzerland.
Probst
A
A
Huber
G
G
D000544:Alzheimer Disease / Q000201:enzymology*; D053829:Amyloid Precursor Protein Secretases; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D016282:Aspartic Acid Endopeptidases; D002401:Cathepsin B / Q000378:metabolism; D003546:Cysteine Endopeptidases / Q000378:metabolism; D010450:Endopeptidases / Q000378:metabolism*; D006801:Humans; D007610:Kallikreins / Q000378:metabolism; D009097:Multienzyme Complexes / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex
D016564:Amyloid beta-Protein Precursor; D009097:Multienzyme Complexes; D053829:Amyloid Precursor Protein Secretases; D010450:Endopeptidases; D007610:Kallikreins; D003546:Cysteine Endopeptidases; D002401:Cathepsin B; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human; D046988:Proteasome Endopeptidase Complex