Abstract

It was recently shown (Sampson et al., Elife 9, 2020) that an amyloidogenic protein, CsgA, present in E. coli biofilms in the gut can trigger Parkinson’s disease in mice. This study emphasizes the possible role of the gut microbiome in modulation (and even initiation) of human neurodegenerative disorders, such as Parkinson’s disease. As the CsgA protein was found to accelerate alpha-synuclein (the key amyloidogenic protein in Parkinson’s disease) amyloid formation in vitro, this result suggests that also other amyloidogenic proteins from gut bacteria, and even from the diet (such as stable allergenic proteins), may be able to affect human protein conformations and thereby modulate amyloid-related diseases. In this review, we summarize what has been reported in terms of in vitro cross-reactivity studies between alpha-synuclein and other amyloidogenic human and non-human proteins. It becomes clear from the limited data that exist that there is a fine line between acceleration and inhibition, but that cross-reactivity is widespread, and it is more common for other proteins (among the studied cases) to accelerate alpha-synuclein amyloid formation than to block it. It is of high importance to expand investigations of cross-reactivity between amyloidogenic proteins to both reveal underlying mechanisms and links between human diseases, as well as to develop new treatments that may be based on an altered gut microbiome.

中文翻译：

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α-突触核蛋白与其他人类和非人类淀粉样蛋白之间的串扰：帕金森病中淀粉样蛋白形成的后果。

 抽象的

最近的研究表明（Sampson 等人， Elife 9，2020 ）肠道大肠杆菌生物膜中存在的淀粉样蛋白 CsgA 可以引发小鼠帕金森病。这项研究强调了肠道微生物组在调节（甚至引发）人类神经退行性疾病（例如帕金森病）中的可能作用。由于发现 CsgA 蛋白在体外可加速 α-突触核蛋白（帕金森病的关键淀粉样蛋白）淀粉样蛋白的形成，因此这一结果表明，来自肠道细菌甚至饮食中的其他淀粉样蛋白（例如稳定的过敏蛋白），可能能够影响人类蛋白质构象，从而调节淀粉样蛋白相关疾病。在这篇综述中，我们总结了 α-突触核蛋白与其他人类和非人类淀粉样蛋白之间的体外交叉反应性研究的报道。从现有的有限数据可以清楚地看出，加速和抑制之间存在细微的界限，但交叉反应广泛存在，并且其他蛋白质（在研究的案例中）加速 α-突触核蛋白淀粉样蛋白形成的情况比加速 α-突触核蛋白淀粉样蛋白形成更常见。阻止它。扩大对淀粉样蛋白之间交叉反应性的研究非常重要，以揭示人类疾病之间的潜在机制和联系，并开发可能基于改变的肠道微生物群的新疗法。