부산대학교 도서관

Amyloids are a class of protein with unique self-aggregation properties, and their aberrant accumulation can lead to cellular dysfunctions associated with neurodegenerative diseases. While genetic and environmental factors can influence amyloid formation, molecular triggers and/or facilitators are not well defined. Growing evidence suggests that non-identical amyloid proteins may accelerate reciprocal amyloid aggregation in a prion-like fashion. While humans encode ~30 amyloidogenic proteins, the gut microbiome also produces functional amyloids. For example, curli are cell surface amyloid proteins abundantly expressed by certain gut bacteria. In mice overexpressing the human amyloid [alpha]-synuclein ([alpha]Syn), we reveal that colonization with curli-producing Escherichia coli promotes [alpha]Syn pathology in the gut and the brain. Curli expression is required for E. coli to exacerbate [alpha]Syn-induced behavioral deficits, including intestinal and motor impairments. Purified curli subunits accelerate [alpha]Syn aggregation in biochemical assays, while oral treatment of mice with a gut-restricted amyloid inhibitor prevents curli-mediated acceleration of pathology and behavioral abnormalities. We propose that exposure to microbial amyloids in the gastrointestinal tract can accelerate [alpha]Syn aggregation and disease in the gut and the brain.
Byline: Timothy R Sampson, Collin Challis, Neha Jain, Anastasiya Moiseyenko, Mark S Ladinsky, Gauri G Shastri, Taren Thron, Brittany D Needham, Istvan Horvath, Justine W Debelius, Stefan Janssen, Rob Knight, [...]