The role of bacterial amyloid curli in Alzheimer's Disease

摘要 淀粉样蛋白的沉积与许多复杂疾病的炎症反应有关， 例如阿尔茨海默氏症(AD)和帕金森氏症。在每种疾病中，淀粉样原纤维积聚。 导致局部发炎。除了人类，细菌也表达淀粉样蛋白。卷曲原纤维 由共生和致病肠道细菌表达，包括大肠杆菌、沙门氏菌 是最具特征的细菌淀粉样蛋白。 淀粉样蛋白，无论是人类的还是细菌的，都不具有核苷酸或氨基酸序列的同源性。 然而，所有淀粉样蛋白单体都折叠成共同的保守的交叉β片状结构，这有助于 原纤维的形成。这种纤细的四级结构对生理和生理的许多方面都很重要 淀粉样蛋白的致病性。有趣的是，少量相同或不同来源的预成型纤维 (例如，人或细菌)已被证明显著加速了单体的聚合过程 淀粉样蛋白进入纤维结构和沉积。这种现象称为播种/交叉播种， 已证明发生在人与人之间的淀粉样蛋白，例如AD的tau淀粉样蛋白和帕金森氏症的-synclein 疾病，或人类-细菌淀粉样蛋白，例如-synclein和Curli。因为人类不断地接触到 细菌产品通过它们的微生物群，以及偶尔接触到的病原菌，很容易 假设人类经常接触细菌淀粉样蛋白。 这项应用的目的是阐明胃肠道中是否存在卷曲纤维。 侵袭性病原体的肠道或全身表现可能参与AD的发病机制。

Summary Deposition of amyloid proteins is associated with inflammatory responses in a number of complex illnesses, such as Alzheimer's disease (AD) and Parkinson's disease. In each disease, an amyloid fibril accumulates resulting in local inflammation. In addition to humans, bacteria also express amyloid proteins. Curli fibrils expressed by the commensal as well as pathogenic enteric bacteria, including Escherichia coli, Salmonella ssp are the best-characterized bacterial amyloids. Amyloid proteins, whether human or bacterial, do not share nucleotide or amino acid sequence homology. Nevertheless, all amyloid monomers fold into a common conserved cross-beta sheet structure, which facilitates the fibril formation. This fibrillar quaternary structure is important for many aspects of the physiology and pathogenicity of amyloid proteins. Intriguingly, small amount of preformed fibrils of the same or different origin (e.g. human or bacterial) have been shown to dramatically accelerate the polymerization process of a monomeric amyloid protein into fibrillar structures and deposits. This phenomenon is known as seeding/cross-seeding and is documented to occur between human-human amyloids, e.g. tau amyloid from AD and -synclein from Parkinson's disease, or human-bacterial amyloids, e.g. -synclein and curli. Since humans are continuously exposed to bacterial products through their microbiomes, as well occasionally exposed to the pathogenic bacteria, it is easy to postulate that humans are constantly exposed to bacterial amyloids. The objective of this application is to elucidate whether the presence of curli fibrils in the gastrointestinal tract or systemic presentation by invasive pathogens could contribute to disease pathogenesis in AD.