The development of preventives and therapeutics for Alzheimer's disease that inhibit the formation of beta-amyloid fibrils (fAbeta), as well as destabilize preformed fAbeta.
The development of preventives and therapeutics for Alzheimer's disease that inhibit the formation of beta-amyloid fibrils (fAbeta), as well as destabilize preformed fAbeta.
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发表时间：
2006
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
脑内主要由淀粉样β蛋白（Abeta）组成的神经炎性斑块是阿尔茨海默病（AD）的早期和不变的神经病理学特征。目前对抗AD药物的研究主要集中在改变脑中Abeta沉积的过程。本文综述了近年来抑制β-淀粉样蛋白原纤维（fAbeta）形成和破坏fAbeta稳定性的分子的研究进展。最近，已经报道了各种化合物如姜黄素、尼古丁和葡萄酒相关多酚在体外在pH 7.5和37 ℃下抑制fAbeta的形成、延伸以及使预先形成的fAbeta不稳定。在细胞培养实验中，不稳定的fAbeta被认为比完整的fAbeta毒性更小。在转基因小鼠模型研究中，一些化合物如姜黄素和尼古丁也被报道在体内减少斑块负荷。尽管这些化合物抑制从Abeta形成fAbeta和使预先形成的fAbeta不稳定的机制仍不清楚，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 beta-protein (Abeta) in the brain are an early and invariant neuropathological feature of Alzheimer's disease (AD). The current search for anti-AD drugs is mainly focused on modification of the process of Abeta deposition in the brain. In this article, the recent development of the molecules that inhibit the formation of beta-amyloid fibrils (fAbeta), as well as destabilize preformed fAbeta is reviewed. Recently, various compounds such as curcumin, nicotine and wine-related polyphenols have been reported to inhibit the formation, extension of fAbeta, as well as destabilize preformed fAbeta at pH 7.5 at 37 degrees C in vitro. In cell culture experiments, destabilized fAbeta were suggested to be less toxic than intact fAbeta. 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 fAbeta formation from Abeta, and destabilize preformed fAbeta are still unclear, they could be key molecules for the development of preventives and therapeutics for AD.