Triiodide ion-induced inhibition of amyloid aggregate formation: A case study of α-synuclein
Triiodide ion-induced inhibition of amyloid aggregate formation: A case study of α-synuclein
复制标题
三碘离子诱导的淀粉样蛋白聚集体形成抑制：α-突触核蛋白的案例研究
DOI：
10.1016/j.molliq.2022.119446
复制
发表时间：
2022
影响因子：
6
通讯作者：
Yoshimura Yukihiro
中科院分区：
文献类型：
--
作者：
Takekiyo Takahiro;Yamada Natsuki;Amo Taku;Asano Atsushi;Yoshimura Yukihiro
抑制淀粉样蛋白形成的小分子化合物对于开发抗淀粉样蛋白生成剂具有重要意义。我们重点介绍了碘化物盐作为体外抗淀粉样蛋白生成剂，广泛应用于片剂、补充剂、消毒剂和药物中。我们采用光学光谱法研究了碘化乙基铵（EAI）作为抗淀粉样蛋白生成剂对人α-突触核蛋白（α-Syn）淀粉样蛋白聚集体（中性pD和310 K）形成的影响。傅立叶变换红外光谱分析和刚果红测定显示，浓缩的EAI溶液可以抑制α-Syn淀粉样蛋白聚集体（α-SynA）的形成。UV-Vis和拉曼光谱表明，在EAI水溶液中有三碘离子（I3-）的形成，并阐明I3-离子与α-Syn N-末端的肽骨架和带正电荷的区域相互作用，从而抑制α-Syn A的形成。除了EAI，碘化铵（NH 4 I）和甲基碘化铵（MAI）也抑制α-SynA：NH 4 I和MAI形成I3−离子。这两种盐的缓蚀能力均强于碱金属碘化物（KI和NaI）。目前的结果表明，碘化铵形成I3−离子有可能成为α-Syn的有效抗淀粉样蛋白生成剂。
Small compounds that inhibit amyloid protein formation are of interest for the development of anti-amyloidogenic agents. We focused on iodide salts, which are widely used in tablets, supplements, disinfectants, and pharmaceuticals, as anti-amyloidogenic agentsin vitro. We performed optical spectroscopy to investigate the effects of ethylammonium iodide (EAI) as an anti-amyloidogenic agent on the formation of amyloid aggregates (neutral pD and 310 K) of human α-synuclein (α-Syn) over a wide range of EAI concentrations. Fourier-transform infrared spectral analysis and a congo red assay revealed that concentrated EAI solutions could inhibit the formation of α-Syn amyloid aggregates (α-SynA). UV–Vis and Raman spectra showed that triiodide (I3−) ion formation occurred in aqueous EAI solution, and clarified that the I3–ion relates to the inhibition of α-SynA formation because of the interactions with the peptide backbone and positively charged region in the N-terminal region of α-Syn. In addition to EAI, ammonium iodide (NH4I) and methylammonium iodide (MAI) also inhibited α-SynA: NH4I and MAI form the I3−ion. The inhibition ability of these two salts are stronger than alkali-iodides (KI and NaI). The present results suggest that ammonium iodides that form I3−ions have the potential to be effective anti-amyloidogenic agents for α-Syn.