Dept. of Pathology, Case Western Reserve University, Cleveland, Ohio, USA.
Brown Cancer Center, University of Louisville School of Medicine, Louisville, Kentucky, USA.
Sci Rep. 2016 Oct 6;6:34477. doi: 10.1038/srep34477.
Misfolded alpha-synuclein (AS) and other neurodegenerative disorder proteins display prion-like transmission of protein aggregation. Factors responsible for the initiation of AS aggregation are unknown. To evaluate the role of amyloid proteins made by the microbiota we exposed aged rats and transgenic C. elegans to E. coli producing the extracellular bacterial amyloid protein curli. Rats exposed to curli-producing bacteria displayed increased neuronal AS deposition in both gut and brain and enhanced microgliosis and astrogliosis compared to rats exposed to either mutant bacteria unable to synthesize curli, or to vehicle alone. Animals exposed to curli producing bacteria also had more expression of TLR2, IL-6 and TNF in the brain than the other two groups. There were no differences among the rat groups in survival, body weight, inflammation in the mouth, retina, kidneys or gut epithelia, and circulating cytokine levels. AS-expressing C. elegans fed on curli-producing bacteria also had enhanced AS aggregation. These results suggest that bacterial amyloid functions as a trigger to initiate AS aggregation through cross-seeding and also primes responses of the innate immune system.
错误折叠的α-突触核蛋白（AS）和其他神经退行性疾病蛋白显示出朊病毒样的蛋白聚集传播。导致 AS 聚集起始的因素尚不清楚。为了评估微生物群产生的淀粉样蛋白的作用，我们使年老的大鼠和转基因秀丽隐杆线虫暴露于产生细胞外细菌淀粉样蛋白 curli 的大肠杆菌中。与暴露于无法合成 curli 的突变细菌或单独载体的大鼠相比，暴露于产生 curli 的细菌的大鼠在肠道和大脑中表现出更多的神经元 AS 沉积，并增强了小胶质细胞和星形胶质细胞增生。与其他两组相比，暴露于产生 curli 的细菌的动物在大脑中的 TLR2、IL-6 和 TNF 表达也更多。三组大鼠在存活率、体重、口腔、视网膜、肾脏或肠道上皮炎症以及循环细胞因子水平方面均无差异。喂食产生 curli 的细菌的表达 AS 的秀丽隐杆线虫也表现出增强的 AS 聚集。这些结果表明，细菌淀粉样蛋白通过交叉成核作为引发 AS 聚集的触发因素，并引发先天免疫系统的反应。
