Involvement of caspases in proteolytic cleavage of Alzheimer's amyloid-beta precursor protein and amyloidogenic A beta peptide formation.
Involvement of caspases in proteolytic cleavage of Alzheimer's amyloid-beta precursor protein and amyloidogenic A beta peptide formation.
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发表时间：
1999
期刊：
影响因子：
64.5
通讯作者：
F. Gervais;D. Xu;G. Robertson;J. Vaillancourt;Y. Zhu;J. Huang;A. LeBlanc;D. Smith;M. Rigby;M. Shearman;E. Clarke;H. Zheng;L. V. D. van der Ploeg;S. C. Ruffolo;N. Thornberry;S. Xanthoudakis;R. Zamboni;S. Roy;D. Nicholson
中科院分区：
文献类型：
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作者：
F. Gervais;D. Xu;G. Robertson;J. Vaillancourt;Y. Zhu;J. Huang;A. LeBlanc;D. Smith;M. Rigby;M. Shearman;E. Clarke;H. Zheng;L. V. D. van der Ploeg;S. C. Ruffolo;N. Thornberry;S. Xanthoudakis;R. Zamboni;S. Roy;D. Nicholson
β-淀粉样蛋白前体蛋白 (APP) 在细胞凋亡过程中被半胱天冬酶直接有效地裂解，导致 β-淀粉样蛋白 (Aβ) 肽形成增加。 Caspase 介导的蛋白水解作用的主要位点位于 APP 的细胞质尾部内，该位点的裂解发生在急性兴奋性毒性或缺血性脑损伤后的体内海马神经元中。 Caspase-3 是参与 APP 裂解的主要 caspase，这与其在阿尔茨海默病大脑死亡神经元中的显着升高以及其 APP 裂解产物与老年斑中的 Aβ 共定位一致。因此，半胱天冬酶似乎在 APP 的蛋白水解过程和由此产生的 Aβ 肽形成倾向以及阿尔茨海默病神经元最终凋亡中发挥双重作用。
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.