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表面等离子体共振在研究构象疾病相关蛋白相互作用中的应用:新治疗视角的实验方法。

The Use of Surface Plasmon Resonance to Study the Interactions of Proteins Involved in Conformational Diseases: Experimental Approaches for New Therapeutical Perspectives.

机构信息

IRCCS-Fondazione Bietti, Rome, Italy.

Chemistry Department, Università di Catania, Viale Andrea Doria 6, 95125, Catania, Italy.

出版信息

Curr Med Chem. 2023;30(36):4072-4095. doi: 10.2174/0929867330666230116162646.

Abstract

In recent years, the scientific community has been trying to tackle different diseases by using unifying and holistic approaches based on the concept that it is possible to target apparently very different diseases under a comprehensive general scheme. In other words, various different diseases have been grouped together under the label of "conformational diseases", because the triggering cause for each malady is the misfolding of a specific protein, whose dyshomeostasis and accumulation cause all the other downhill biomolecular events characteristic of each different disease. In a parallel manner, analytical techniques have developed to investigate protein misfolding and accumulation, so as to give a valid technical support to the investigation of conformational diseases. In this scenario, surface plasmon resonance (SPR) has widely contributed to study many different aspects correlated to conformational diseases, offering the advantages of real time investigations, use of small amounts of biological materials and possibility to mimic the cellular environments without recurring to the use of fluorescent tags. In this review, after a brief introduction about conformational diseases and the SPR technique, a thorough description of the various uses of SPR to investigate the biomolecular mechanisms involved in these diseases is given in order to provide the reader with an exhaustive list as well as a critical perspective of the use of SPR for such topic. The case of Alzheimer's disease is discussed at a deeper level. We hope that this work will make the reader aware of all the possible SPR experimental approaches, which can be used to develop new possible therapeutic strategies to tackle conformational diseases.

摘要

近年来,科学界一直试图通过使用基于统一和整体的方法来治疗各种疾病,这些方法基于这样一种概念,即有可能在一个全面的总体方案下针对明显非常不同的疾病进行靶向治疗。换句话说,各种不同的疾病已被归为“构象疾病”,因为每种疾病的触发原因都是特定蛋白质的错误折叠,其失调和积累导致了每种不同疾病特有的所有其他生物分子事件的恶化。以类似的方式,分析技术已经发展起来以研究蛋白质错误折叠和积累,从而为构象疾病的研究提供有效的技术支持。在这种情况下,表面等离子体共振(SPR)技术广泛应用于研究与构象疾病相关的许多不同方面,具有实时研究、使用少量生物材料以及在不使用荧光标记的情况下模拟细胞环境的可能性等优点。在这篇综述中,在简要介绍构象疾病和 SPR 技术之后,详细描述了 SPR 在研究这些疾病中涉及的生物分子机制的各种用途,以便为读者提供一个详尽的列表以及对 SPR 用于此类主题的批判性观点。阿尔茨海默病的情况进行了更深入的讨论。我们希望这项工作能使读者了解所有可能的 SPR 实验方法,这些方法可用于开发新的可能的治疗策略来应对构象疾病。

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