Details

Autor(en) / Beteiligte

• 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.

Titel

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

Ist Teil von

• Cell, 1999-04, Vol.97 (3), p.395-406

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

1999

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.