The Development of Preventives and Therapeutics for Alzheimers Disease that Inhibit the Formation of β-Amyloid Fibrils (fAβ), as Well as Destabilize Preformed fAβ
The Development of Preventives and Therapeutics for Alzheimers Disease that Inhibit the Formation of β-Amyloid Fibrils (fAβ), as Well as Destabilize Preformed fAβ
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DOI：
10.2174/138161206778793010
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发表时间：
2006-10
影响因子：
3.1
通讯作者：
K. Ono;H. Naiki;M. Yamada
中科院分区：
文献类型：
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作者：
K. Ono;H. Naiki;M. Yamada
大脑中主要由β淀粉样蛋白（Aβ）组成的神经炎斑块是阿尔茨海默病（AD）的早期且不变的神经病理学特征。目前抗 AD 药物的研究主要集中在改变 Aβ 在大脑中沉积的过程。在本文中，综述了抑制 β-淀粉样原纤维 (fAβ) 形成以及破坏预先形成的 fAβ 稳定性的分子的最新进展。最近，据报道，姜黄素、尼古丁和与葡萄酒相关的多酚等多种化合物可以抑制 fAβ 的形成和延伸，并在 37°C 和 pH 7.5 的体外条件下破坏预先形成的 fAβ 的稳定性。在细胞培养实验中，不稳定的 fAβ 被认为比完整的 fAβ 毒性更低。在转基因小鼠模型研究中，姜黄素和尼古丁等一些化合物也被报道可以减少体内斑块负担。尽管这些化合物抑制 Aβ 形成 fAβ 并破坏预先形成的 fAβ 稳定性的机制尚不清楚，但它们可能是开发 AD 预防和治疗药物的关键分子。
Neuritic plaques composed mainly of amyloid β-protein (Aβ) in the brain are an early and invariant neuropathological feature of Alzheimers disease (AD). The current search for anti-AD drugs is mainly focused on modification of the process of Aβ deposition in the brain. In this article, the recent development of the molecules that inhibit the formation of β-amyloid fibrils (fAβ), as well as destabilize preformed fAβ is reviewed. Recently, various compounds such as curcumin, nicotine and wine-related polyphenols have been reported to inhibit the formation, extension of fAβ, as well as destabilize preformed fAβ at pH 7.5 at 37°C in vitro. In cell culture experiments, destabilized fAβ were suggested to be less toxic than intact fAβ. In transgenic mice model study, some coumpounds such as curcumin and nicotine have also been reported to reduce plaque burden in vivo. Although the mechanisms by which these compounds inhibit fAβ formation from Aβ, and destabilize preformed fAβ are still unclear, they could be key molecules for the development of preventives and therapeutics for AD.