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一种钌功能化的金属有机框架纳米酶作为β-淀粉样蛋白聚集体的抑制剂和解聚剂。

A Ru-functionalized-NMOF nanozyme as an inhibitor and disaggregator of β-amyloid aggregates.

作者信息

Luo Wan-Chun, Bao Li-Na, Zhang Yu, Zhang Zi-Tong, Li Xi, Pan Meng-Meng, Zhang Jin-Tao, Huang Kun, Xu Yu, Xu Li

机构信息

Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan 430030, China.

出版信息

J Mater Chem B. 2024 Dec 4;12(47):12239-12250. doi: 10.1039/d4tb01313a.

Abstract

Alzheimer's disease (AD) heavily impacts human lives and is becoming serious as societies age. Inhibiting and disaggregating β-amyloid aggregates is a possible solution for AD therapy. In this study, a novel type of nanozyme based on Ru-chelated nanoscale metal organic frameworks (Ru-NMOFs), displaying strong peroxidase-like activity, was proposed as an inhibitor and disaggregator of β-amyloid aggregates. As a high concentration of hydrogen peroxide is present at the sites of β-amyloid aggregates, Ru-NMOFs could catalyze the conversion of hydrogen peroxide to hydroxyl radicals. Thus, these hydroxyl radicals would attack the β-amyloid chain, oxidizing it to enhance its hydrophilicity, which results in a decreased hydrophobic interaction and reduced degree of aggregation. Ru-NMOFs could effectively inhibit as well as disaggregate β-amyloid fibrils both and . Additionally, the reduction of the β-amyloid aggregates and the attenuation of reactive oxygen species transfer led to lower levels of inflammatory factors, which could be beneficial in alleviating AD symptoms. In a typical treatment, Ru-NMOFs could mitigate the paralysis of CL2120 and elevate survival rates. This study opens a new avenue for MOF-based nanozymes as potential treatment agents for AD therapy.

摘要

阿尔茨海默病(AD)严重影响人类生活,且随着社会老龄化问题日益严峻。抑制和分解β-淀粉样蛋白聚集体是治疗AD的一种可能解决方案。在本研究中,一种基于钌螯合纳米级金属有机框架(Ru-NMOFs)的新型纳米酶被提出作为β-淀粉样蛋白聚集体的抑制剂和解聚剂,该纳米酶具有很强的过氧化物酶样活性。由于在β-淀粉样蛋白聚集体部位存在高浓度的过氧化氢,Ru-NMOFs可以催化过氧化氢转化为羟基自由基。因此,这些羟基自由基会攻击β-淀粉样蛋白链,将其氧化以增强其亲水性,从而导致疏水相互作用减弱和聚集程度降低。Ru-NMOFs在体内和体外均能有效抑制和解聚β-淀粉样蛋白纤维。此外,β-淀粉样蛋白聚集体的减少和活性氧转移的减弱导致炎症因子水平降低,这可能有助于缓解AD症状。在典型治疗中,Ru-NMOFs可以减轻CL2120的麻痹并提高存活率。本研究为基于金属有机框架的纳米酶作为AD治疗的潜在治疗剂开辟了一条新途径。

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