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Inhibition of amyloid formation of amyloid β (1-42), amylin and insulin by 1,5-diazacyclooctanes, a spermine-acrolein conjugate
Bioorganic & Medicinal Chemistry ( IF 3.3 ) Pub Date : 2021-08-28 , DOI: 10.1016/j.bmc.2021.116391
Risako Kunitomi 1 , Ambara R Pradipta 2 , Haruka Kawabe 1 , Nadine Lobsiger 3 , Katsunori Tanaka 4 , Tamotsu Zako 1
Affiliation  

Amyloid aggregates of proteins are known to be involved in various diseases such as Alzheimer's disease (AD). It is therefore speculated that the inhibition of amyloid formation can play an important role in the prevention of various diseases involving amyloids. Recently, we have found that acrolein reacts with polyamines, such as spermine, and produces 1,5-diazacyclooctane, such as cyclic spermine (cSPM). cSPM could suppress the aggregation of amyloid β 1-40 (Aβ40), one of the causative proteins of AD. This result suggests the potential inhibitory effect of cSPM against Aβ 1-42 (Aβ42) and other amyloid protein aggregation which are the main pathological features of AD and other diseases. However, the effect on the aggregation of such proteins remains unclear. In this study, the effect of cSPM on the amyloid formation of Aβ42, amylin, and insulin was investigated. These three amyloidogenic proteins forming amyloids under physiological conditions (pH 7.4 and 37℃) served as model and are thought to be the causative proteins of AD, type 2 diabetes, and insulin-derived amyloidosis, respectively. Our results indicate that cSPM can suppress the amyloid aggregation of these proteins and reduce cytotoxicity. This study contributes to a better understanding of means to potentially counteract diseases by the means of polyamine and acrolein.



中文翻译:

通过 1,5-二氮杂环辛烷(一种精胺-丙烯醛偶联物)抑制淀粉样蛋白 β (1-42)、胰淀素和胰岛素的淀粉样蛋白形成

已知蛋白质的淀粉样蛋白聚集体涉及多种疾病,例如阿尔茨海默病 (AD)。因此推测抑制淀粉样蛋白的形成可以在预防各种涉及淀粉样蛋白的疾病中发挥重要作用。最近,我们发现丙烯醛与多胺(如精胺)反应,生成 1,5-二氮杂环辛烷,如环精胺 (cSPM)。cSPM 可以抑制淀粉样蛋白 β 1-40 (Aβ40) 的聚集,这是 AD 的致病蛋白之一。该结果表明 cSPM 对 Aβ 1-42 (Aβ42) 和其他淀粉样蛋白聚集具有潜在抑制作用,这些聚集是 AD 和其他疾病的主要病理特征。然而,对这些蛋白质聚集的影响仍不清楚。在本研究中,cSPM 对 Aβ42、胰淀素、并研究了胰岛素。这三种在生理条件下(pH 7.4 和 37℃)形成淀粉样蛋白的淀粉样蛋白作为模型,被认为分别是 AD、2 型糖尿病和胰岛素衍生淀粉样变性的致病蛋白。我们的结果表明 cSPM 可以抑制这些蛋白质的淀粉样蛋白聚集并降低细胞毒性。这项研究有助于更好地了解通过多胺和丙烯醛潜在地对抗疾病的方法。我们的结果表明 cSPM 可以抑制这些蛋白质的淀粉样蛋白聚集并降低细胞毒性。这项研究有助于更好地了解通过多胺和丙烯醛潜在地对抗疾病的方法。我们的结果表明 cSPM 可以抑制这些蛋白质的淀粉样蛋白聚集并降低细胞毒性。这项研究有助于更好地了解通过多胺和丙烯醛潜在地对抗疾病的方法。

更新日期:2021-08-29
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