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

Producción científica: Contribución a una revistaArtículorevisión exhaustiva

754 Citas (Scopus)

Resumen

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.

Idioma originalEnglish
Páginas (desde-hasta)395-406
Número de páginas12
PublicaciónCell
Volumen97
N.º3
DOI
EstadoPublished - abr. 30 1999
Publicado de forma externa

ASJC Scopus Subject Areas

  • General Biochemistry,Genetics and Molecular Biology

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