Department of Biology and Biological Engineering, Chalmers University of Technology, Gothenburg, Sweden.
J Parkinsons Dis. 2020;10(3):819-830. doi: 10.3233/JPD-202085.
It was recently shown (Sampson et al., Elife9, 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.
最近有研究表明（Sampson 等人，Elife9，2020），存在于肠道中生物膜中的一种淀粉样蛋白 CsgA 可以在小鼠中引发帕金森病。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（如帕金森病）方面的可能作用。由于 CsgA 蛋白被发现能够在体外加速α-突触核蛋白（帕金森病的关键淀粉样蛋白）的淀粉样形成，这一结果表明，来自肠道细菌的其他淀粉样蛋白，甚至来自饮食（如稳定的过敏原蛋白），也可能能够影响人类蛋白质构象，从而调节与淀粉样蛋白相关的疾病。在这篇综述中，我们总结了在体外α-突触核蛋白与其他淀粉样蛋白人类和非人类蛋白质之间的交叉反应性研究中已经报道的内容。从现有的有限数据中可以清楚地看出，加速和抑制之间存在着细微的差别，但交叉反应很普遍，在已研究的案例中，其他蛋白质加速α-突触核蛋白淀粉样形成的情况比阻止它的情况更为常见。扩大对淀粉样蛋白之间交叉反应性的研究对于揭示人类疾病之间的潜在机制和联系以及开发可能基于改变肠道微生物组的新治疗方法非常重要。
