PMID- 10319819
OWN - NLM
STAT- MEDLINE
DCOM- 19990520
LR  - 20190705
IS  - 0092-8674 (Print)
IS  - 0092-8674 (Linking)
VI  - 97
IP  - 3
DP  - 1999 Apr 30
TI  - Involvement of caspases in proteolytic cleavage of Alzheimer's amyloid-beta
      precursor protein and amyloidogenic A beta peptide formation.
PG  - 395-406
AB  - The amyloid-beta precursor protein (APP) is directly and efficiently cleaved by
      caspases during apoptosis, resulting in elevated amyloid-beta (A beta) 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 A beta in senile plaques. Caspases thus appear to
      play a dual role in proteolytic processing of APP and the resulting propensity
      for A beta peptide formation, as well as in the ultimate apoptotic death of
      neurons in Alzheimer's disease.
FAU - Gervais, F G
AU  - Gervais FG
AD  - Department of Pharmacology, Biochemistry, and Molecular Biology, Merck Frosst
      Centre for Therapeutic Research, Merck Research Laboratories, Kirkland, Quebec,
      Canada.
FAU - Xu, D
AU  - Xu D
FAU - Robertson, G S
AU  - Robertson GS
FAU - Vaillancourt, J P
AU  - Vaillancourt JP
FAU - Zhu, Y
AU  - Zhu Y
FAU - Huang, J
AU  - Huang J
FAU - LeBlanc, A
AU  - LeBlanc A
FAU - Smith, D
AU  - Smith D
FAU - Rigby, M
AU  - Rigby M
FAU - Shearman, M S
AU  - Shearman MS
FAU - Clarke, E E
AU  - Clarke EE
FAU - Zheng, H
AU  - Zheng H
FAU - Van Der Ploeg, L H
AU  - Van Der Ploeg LH
FAU - Ruffolo, S C
AU  - Ruffolo SC
FAU - Thornberry, N A
AU  - Thornberry NA
FAU - Xanthoudakis, S
AU  - Xanthoudakis S
FAU - Zamboni, R J
AU  - Zamboni RJ
FAU - Roy, S
AU  - Roy S
FAU - Nicholson, D W
AU  - Nicholson DW
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cell
JT  - Cell
JID - 0413066
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (Amyloid beta-Protein Precursor)
RN  - 0 (Cysteine Proteinase Inhibitors)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Enzyme Precursors)
RN  - 0 (Excitatory Amino Acid Agonists)
RN  - 0 (Oligopeptides)
RN  - 0 (acetyl-aspartyl-glutamyl-valyl-aspartal)
RN  - 143313-51-3 (L 709049)
RN  - 30KYC7MIAI (Aspartic Acid)
RN  - EC 3.4.- (Amyloid Precursor Protein Secretases)
RN  - EC 3.4.- (Endopeptidases)
RN  - EC 3.4.22.- (CASP3 protein, human)
RN  - EC 3.4.22.- (Casp3 protein, mouse)
RN  - EC 3.4.22.- (Casp3 protein, rat)
RN  - EC 3.4.22.- (Caspase 3)
RN  - EC 3.4.22.- (Caspases)
RN  - EC 3.4.23.- (Aspartic Acid Endopeptidases)
RN  - EC 3.4.23.46 (BACE1 protein, human)
RN  - EC 3.4.23.46 (Bace1 protein, mouse)
RN  - SIV03811UC (Kainic Acid)
RN  - XT3Z54Z28A (Camptothecin)
SB  - IM
MH  - Acute Disease
MH  - Alzheimer Disease/*enzymology/genetics/pathology
MH  - Amyloid Precursor Protein Secretases
MH  - Amyloid beta-Peptides/genetics/*metabolism
MH  - Amyloid beta-Protein Precursor/genetics/*metabolism
MH  - Amyloidosis/*enzymology/genetics/pathology
MH  - Animals
MH  - Apoptosis/drug effects/genetics
MH  - Aspartic Acid
MH  - Aspartic Acid Endopeptidases
MH  - Brain Diseases/chemically induced/enzymology/pathology
MH  - Camptothecin/pharmacology
MH  - Caspase 3
MH  - Caspases/analysis/*metabolism
MH  - Cysteine Proteinase Inhibitors/pharmacology
MH  - Endopeptidases/genetics
MH  - Enzyme Inhibitors/pharmacology
MH  - Enzyme Precursors/analysis/metabolism
MH  - Excitatory Amino Acid Agonists
MH  - Hippocampus/cytology
MH  - Humans
MH  - In Situ Nick-End Labeling
MH  - Kainic Acid
MH  - Leukemia, Erythroblastic, Acute
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mutation/physiology
MH  - Neurons/chemistry/cytology/enzymology
MH  - Oligopeptides/pharmacology
MH  - Rabbits
MH  - Rats
MH  - Rats, Wistar
MH  - Sweden
MH  - Tumor Cells, Cultured
EDAT- 1999/05/13 00:00
MHDA- 1999/05/13 00:01
CRDT- 1999/05/13 00:00
PHST- 1999/05/13 00:00 [pubmed]
PHST- 1999/05/13 00:01 [medline]
PHST- 1999/05/13 00:00 [entrez]
AID - S0092-8674(00)80748-5 [pii]
AID - 10.1016/s0092-8674(00)80748-5 [doi]
PST - ppublish
SO  - Cell. 1999 Apr 30;97(3):395-406. doi: 10.1016/s0092-8674(00)80748-5.