Effect of metals on kinetic pathways of amyloid-β aggregation.
Effect of metals on kinetic pathways of amyloid-β aggregation.
复制标题
DOI：
10.3390/biom4010101
复制
发表时间：
2014-01-10
期刊：
影响因子：
5.5
通讯作者：
Leonenko Z
中科院分区：
文献类型：
--
作者：
Hane F;Leonenko Z
包括铜和锌在内的金属离子通过多种机制参与阿尔茨海默病的发病机制，包括增加淀粉样蛋白与β的亲和力和氧化还原效应。最近的报告表明，淀粉样蛋白-β单体不一定通过最终的中间途径到达稳定的淀粉样原纤维结构。相反，淀粉样蛋白-β错误折叠可能遵循各种途径，导致纤维状最终产物或具有不同结构和大小的各种寡聚体最终产物。金属离子的存在已被证明改变了淀粉样蛋白-β多肽的动力学途径，这可能导致更多有毒的寡聚体最终产物。在这项工作中，我们回顾了支持这一假说的当代文献，即金属离子改变了淀粉样蛋白-β错误折叠的反应途径，导致更多的神经毒性物种。
Metal ions, including copper and zinc, have been implicated in the pathogenesis of Alzheimer’s disease through a variety of mechanisms including increased amyloid-β affinity and redox effects. Recent reports have demonstrated that the amyloid-β monomer does not necessarily travel through a definitive intermediary en-route to a stable amyloid fibril structure. Rather, amyloid-β misfolding may follow a variety of pathways resulting in a fibrillar end-product or a variety of oligomeric end-products with a diversity of structures and sizes. The presence of metal ions has been demonstrated to alter the kinetic pathway of the amyloid-β peptide which may lead to more toxic oligomeric end-products. In this work, we review the contemporary literature supporting the hypothesis that metal ions alter the reaction pathway of amyloid-β misfolding leading to more neurotoxic species.