A second cytotoxic proteolytic peptide derived from amyloid beta-protein precursor.
The amyloid beta-protein precursor gives rise to the amyloid beta-protein, the principal constituent of senile plaques and a cytotoxic fragment involved in the pathogenesis of Alzheimer disease. Here we show that amyloid beta-protein precursor was proteolytically cleaved by caspases in the C terminus to generate a second unrelated peptide, called C31. The resultant C31 peptide was a potent inducer of apoptosis. Both caspase-cleaved amyloid beta-protein precursor and activated caspase-9 were present in brains of Alzheimer disease patients but not in control brains. These findings indicate the possibility that caspase cleavage of amyloid beta-protein precursor with the generation of C31 may be involved in the neuronal death associated with Alzheimer disease.
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Program on Aging, The Burnham Institute, La Jolla, California 92037, USA.
Rabizadeh
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S
Chandra
S
S
Shayya
R F
RF
Ellerby
L M
LM
Ye
X
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Salvesen
G S
GS
Koo
E H
EH
Bredesen
D E
DE
D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis; D001921:Brain / Q000201:enzymology / Q000473:pathology; D053453:Caspase 9; D020169:Caspases / Q000235:genetics / Q000378:metabolism*; D002461:Cell Line, Transformed; D004789:Enzyme Activation; D006801:Humans; D051379:Mice; D010446:Peptide Fragments / Q000378:metabolism; D010455:Peptides / Q000378:metabolism* / Q000502:physiology; D013379:Substrate Specificity
D016564:Amyloid beta-Protein Precursor; D010446:Peptide Fragments; D010455:Peptides; C092826:amyloid precursor protein, carboxy-terminal 100 residues; C506433:CASP9 protein, human; C506434:Casp9 protein, mouse; D053453:Caspase 9; D020169:Caspases