Involvement of caspases in proteolytic cleavage of Alzheimer's amyloid-β precursor protein and amyloidogenic Aβ peptide formation

François G. Gervais; Daigen Xu; George S. Robertson; John P. Vaillancourt; Yanxia Zhu; Jing Qi Huang; Andréa LeBlanc; David Smith; Michael Rigby; Mark S. Shearman; Earl E. Clarke; Hui Zheng; Leonardus H.T. Van Der Ploeg; Salvatore C. Ruffolo; Nancy A. Thornberry; Steve Xanthoudakis; Robert J. Zamboni; Sophie Roy; Donald W. Nicholson

doi:10.1016/S0092-8674(00)80748-5

Involvement of caspases in proteolytic cleavage of Alzheimer's amyloid-β precursor protein and amyloidogenic Aβ peptide formation

François G. Gervais, Daigen Xu, George S. Robertson, John P. Vaillancourt, Yanxia Zhu, Jing Qi Huang, Andréa LeBlanc, David Smith, Michael Rigby, Mark S. Shearman, Earl E. Clarke, Hui Zheng, Leonardus H.T. Van Der Ploeg, Salvatore C. Ruffolo, Nancy A. Thornberry, Steve Xanthoudakis, Robert J. Zamboni, Sophie Roy, Donald W. Nicholson

Research output: Contribution to journal › Article › peer-review

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Abstract

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.

Original language	English
Pages (from-to)	395-406
Number of pages	12
Journal	Cell
Volume	97
Issue number	3
DOIs	https://doi.org/10.1016/S0092-8674(00)80748-5
Publication status	Published - Apr 30 1999
Externally published	Yes

ASJC Scopus Subject Areas

General Biochemistry,Genetics and Molecular Biology

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10.1016/S0092-8674(00)80748-5

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Gervais, F. G., Xu, D., Robertson, G. S., Vaillancourt, J. P., Zhu, Y., Huang, J. Q., LeBlanc, A., Smith, D., Rigby, M., Shearman, M. S., Clarke, E. E., Zheng, H., Van Der Ploeg, L. H. T., Ruffolo, S. C., Thornberry, N. A., Xanthoudakis, S., Zamboni, R. J., Roy, S., & Nicholson, D. W. (1999). Involvement of caspases in proteolytic cleavage of Alzheimer's amyloid-β precursor protein and amyloidogenic Aβ peptide formation. Cell, 97(3), 395-406. https://doi.org/10.1016/S0092-8674(00)80748-5

Gervais, FG, Xu, D, Robertson, GS, Vaillancourt, JP, Zhu, Y, Huang, JQ, LeBlanc, A, Smith, D, Rigby, M, Shearman, MS, Clarke, EE, Zheng, H, Van Der Ploeg, LHT, Ruffolo, SC, Thornberry, NA, Xanthoudakis, S, Zamboni, RJ, Roy, S & Nicholson, DW 1999, 'Involvement of caspases in proteolytic cleavage of Alzheimer's amyloid-β precursor protein and amyloidogenic Aβ peptide formation', Cell, vol. 97, no. 3, pp. 395-406. https://doi.org/10.1016/S0092-8674(00)80748-5

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title = "Involvement of caspases in proteolytic cleavage of Alzheimer's amyloid-β precursor protein and amyloidogenic Aβ peptide formation",

abstract = "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.",

author = "Gervais, {Fran{\c c}ois G.} and Daigen Xu and Robertson, {George S.} and Vaillancourt, {John P.} and Yanxia Zhu and Huang, {Jing Qi} and Andr{\'e}a LeBlanc and David Smith and Michael Rigby and Shearman, {Mark S.} and Clarke, {Earl E.} and Hui Zheng and {Van Der Ploeg}, {Leonardus H.T.} and Ruffolo, {Salvatore C.} and Thornberry, {Nancy A.} and Steve Xanthoudakis and Zamboni, {Robert J.} and Sophie Roy and Nicholson, {Donald W.}",

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AU - Gervais, François G.

AU - Xu, Daigen

AU - Robertson, George S.

AU - Vaillancourt, John P.

AU - Zhu, Yanxia

AU - Huang, Jing Qi

AU - LeBlanc, Andréa

AU - Smith, David

AU - Rigby, Michael

AU - Shearman, Mark S.

AU - Clarke, Earl E.

AU - Zheng, Hui

AU - Van Der Ploeg, Leonardus H.T.

AU - Ruffolo, Salvatore C.

AU - Thornberry, Nancy A.

AU - Xanthoudakis, Steve

AU - Zamboni, Robert J.

AU - Roy, Sophie

AU - Nicholson, Donald W.

PY - 1999/4/30

Y1 - 1999/4/30

N2 - 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.

AB - 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.

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Involvement of caspases in proteolytic cleavage of Alzheimer's amyloid-β precursor protein and amyloidogenic Aβ peptide formation

Abstract

ASJC Scopus Subject Areas

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