A second cytotoxic proteolytic peptide derived from amyloid beta-protein precursor.
A second cytotoxic proteolytic peptide derived from amyloid beta-protein precursor.
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发表时间：
2000
期刊：
影响因子：
82.9
通讯作者：
D. Lu;S. Rabizadeh;S. Chandra;R. Shayya;L. Ellerby;X. Ye;G. Salvesen;E. Koo;D. Bredesen
中科院分区：
文献类型：
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作者：
D. Lu;S. Rabizadeh;S. Chandra;R. Shayya;L. Ellerby;X. Ye;G. Salvesen;E. Koo;D. Bredesen
β-淀粉样蛋白前体产生β-淀粉样蛋白，它是老年斑的主要成分，也是参与阿尔茨海默病发病机制的细胞毒性片段。在这里，我们证明淀粉样蛋白 β 蛋白前体被 C 末端的半胱天冬酶进行蛋白水解切割，生成第二个不相关的肽，称为 C31。所得的 C31 肽是细胞凋亡的有效诱导剂。 caspase 裂解的淀粉样蛋白 β 蛋白前体和激活的 caspase-9 均存在于阿尔茨海默病患者的大脑中，但不存在于对照大脑中。这些发现表明，半胱天冬酶对淀粉样蛋白 β 蛋白前体的裂解以及 C31 的产生可能与阿尔茨海默病相关的神经元死亡有关。
The amyloid beta-protein precursor gives rise to the amyloid beta-protein, the principal constituent of senile plaques and a cytotoxic fragment involved in the pathogenesis of Alzheimer disease. Here we show that amyloid beta-protein precursor was proteolytically cleaved by caspases in the C terminus to generate a second unrelated peptide, called C31. The resultant C31 peptide was a potent inducer of apoptosis. Both caspase-cleaved amyloid beta-protein precursor and activated caspase-9 were present in brains of Alzheimer disease patients but not in control brains. These findings indicate the possibility that caspase cleavage of amyloid beta-protein precursor with the generation of C31 may be involved in the neuronal death associated with Alzheimer disease.