Recent Development of Bifunctional Small Molecules to Study Metal-Amyloid-β Species in Alzheimer's Disease.
Recent Development of Bifunctional Small Molecules to Study Metal-Amyloid-β Species in Alzheimer's Disease.
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DOI：
10.4061/2011/623051
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发表时间：
2010-12-08
影响因子：
--
通讯作者：
Lim MH
中科院分区：
文献类型：
--
作者：
Braymer JJ;Detoma AS;Choi JS;Ko KS;Lim MH
阿尔茨海默氏病（AD）是一种多因素的神经退行性疾病，与大脑中聚集的淀粉样蛋白β（Aβ）辣椒的沉积有关。 （II）和Zn（ii）在解剖大脑的Aβ斑块中发现与Aβ结合，并与聚集和神经毒性联系在一起。然而，发病机理尚不确定，以加速该区域的理解并有助于治疗性发育，最近使用基于合理的结构设计来制作可针对与Aβ相关的金属离子的合适化学试剂（金属螯合）在同一分子中的Aβ相互作用）。讨论其应用作为化学工具和/或潜在疗法的进展。
Alzheimer's disease (AD) is a multifactorial neurodegenerative disease related to the deposition of aggregated amyloid-β (Aβ) peptides in the brain. It has been proposed that metal ion dyshomeostasis and miscompartmentalization contribute to AD progression, especially as metal ions (e.g., Cu(II) and Zn(II)) found in Aβ plaques of the diseased brain can bind to Aβ and be linked to aggregation and neurotoxicity. The role of metal ions in AD pathogenesis, however, is uncertain. To accelerate understanding in this area and contribute to therapeutic development, recent efforts to devise suitable chemical reagents that can target metal ions associated with Aβ have been made using rational structure-based design that combines two functions (metal chelation and Aβ interaction) in the same molecule. This paper presents bifunctional compounds developed by two different design strategies (linkage or incorporation) and discusses progress in their applications as chemical tools and/or potential therapeutics.