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牛磺酸-碳水化合物衍生物可刺激淀粉样β纤维形成并减少阿尔茨海默病样行为。

Taurine-Carbohydrate Derivative Stimulates Fibrillogenesis of Amyloid-β and Reduce Alzheimer-Like Behaviors.

机构信息

Department of pharmacy and Integrated Science and Engineering, Yonsei University, 85 Songdogwahak-ro, Yeonsu-gu, Incheon, 21983, South Korea.

Brain Science Institute, Korea Institute of Science and Technology (KIST) Hwarangno 24-gil 5, Seongbuk-gu, Seoul, 02792, South Korea.

出版信息

Adv Exp Med Biol. 2017;975 Pt 1:225-232. doi: 10.1007/978-94-024-1079-2_20.

Abstract

Amyloid-β (Aβ) aggregates are a hallmark of Alzheimer's disease (AD). Through the misfolding process of Aβ in the brain, oligomeric forms of Aβ accumulate and significantly damage the brain cells inducing neuronal loss and cognitive dysfunctions that lead to AD. We hypothesized that decrease in Aβ oligomers during the aggregation process might be able to reduce Aβ-dependent brain damage. As taurine-like chemicals are often reported to have direct binding abilities to Aβ, we prepared a chemical library that consisted of taurine-carbohydrate derivatives to search for molecules that target Aβ and accelerate its fibrillogenesis. Here, we report that 1-deoxy-1-(2-sulfoethylamino)-D-fructose stimulates the formation of relatively less toxic Aβ fibrils leading to prevention of cognitive deficits in AD acute model mice.

摘要

淀粉样蛋白-β (Aβ) 聚集体是阿尔茨海默病 (AD) 的一个标志。通过大脑中 Aβ 的错误折叠过程,Aβ 的寡聚形式积累并显著损害脑细胞,导致神经元丧失和认知功能障碍,从而导致 AD。我们假设在聚集过程中减少 Aβ 寡聚体可能能够减轻 Aβ 依赖性脑损伤。由于牛磺酸样化学物质通常被报道具有直接与 Aβ 结合的能力,我们制备了一个由牛磺酸-碳水化合物衍生物组成的化学文库,以寻找靶向 Aβ 并加速其纤维化的分子。在这里,我们报告 1-脱氧-1-(2-磺乙基氨基)-D-果糖刺激相对毒性较小的 Aβ 纤维的形成,从而防止 AD 急性模型小鼠的认知缺陷。

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