Involvement of Caspases in Proteolytic Cleavage of Alzheimer’s Amyloid-β Precursor Protein and Amyloidogenic Aβ Peptide Formation

The amyloid-β precursor protein (APP) is directly and efficiently cleaved by caspases during apoptosis, resulting in elevated amyloid-β (Aβ) peptide formation. The predominant site of caspase-mediated proteolysis is within the cytoplasmic tail of APP, and cleavage at this site occurs in hippocampal...

Full description

Saved in:

Bibliographic Details
Published in:	Cell Vol. 97; no. 3; pp. 395 - 406
Main Authors:	Gervais, François G., Xu, Daigen, Robertson, George S., Vaillancourt, John P., Zhu, Yanxia, Huang, JingQi, LeBlanc, Andréa, Smith, David, Rigby, Michael, Shearman, Mark S., Clarke, Earl E., Zheng, Hui, Van Der Ploeg, Leonardus H.T., Ruffolo, Salvatore C., Thornberry, Nancy A., Xanthoudakis, Steve, Zamboni, Robert J., Roy, Sophie, Nicholson, Donald W.
Format:	Journal Article
Language:	English
Published:	United States Elsevier Inc 30-04-1999
Subjects:	Acute Disease Alzheimer Disease - enzymology Alzheimer Disease - genetics Alzheimer Disease - pathology Amyloid beta-Peptides - genetics Amyloid beta-Peptides - metabolism Amyloid beta-Protein Precursor - genetics Amyloid beta-Protein Precursor - metabolism Amyloid Precursor Protein Secretases Amyloidosis - enzymology Amyloidosis - genetics Amyloidosis - pathology Animals Apoptosis - drug effects Apoptosis - genetics Aspartic Acid Aspartic Acid Endopeptidases Brain Diseases - chemically induced Brain Diseases - enzymology Brain Diseases - pathology Camptothecin - pharmacology Caspase 3 Caspases - analysis Caspases - metabolism Cysteine Proteinase Inhibitors - pharmacology Endopeptidases - genetics Enzyme Inhibitors - pharmacology Enzyme Precursors - analysis Enzyme Precursors - metabolism Excitatory Amino Acid Agonists Hippocampus - cytology Humans In Situ Nick-End Labeling Kainic Acid Leukemia, Erythroblastic, Acute Male Mice Mice, Inbred C57BL Mutation - physiology Neurons - chemistry Neurons - cytology Neurons - enzymology Oligopeptides - pharmacology Rabbits Rats Rats, Wistar Sweden Tumor Cells, Cultured Sweden
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	The amyloid-β precursor protein (APP) is directly and efficiently cleaved by caspases during apoptosis, resulting in elevated amyloid-β (Aβ) peptide formation. The predominant site of caspase-mediated proteolysis is within the cytoplasmic tail of APP, and cleavage at this site occurs in hippocampal neurons in vivo following acute excitotoxic or ischemic brain injury. Caspase-3 is the predominant caspase involved in APP cleavage, consistent with its marked elevation in dying neurons of Alzheimer’s disease brains and colocalization of its APP cleavage product with Aβ in senile plaques. Caspases thus appear to play a dual role in proteolytic processing of APP and the resulting propensity for Aβ peptide formation, as well as in the ultimate apoptotic death of neurons in Alzheimer’s disease.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23
ISSN:	0092-8674 1097-4172
DOI:	10.1016/S0092-8674(00)80748-5