| First Author | Sampson TR | Year | 2020 |
| Journal | Elife | Volume | 9 |
| PubMed ID | 32043464 | Mgi Jnum | J:291940 |
| Mgi Id | MGI:6443004 | Doi | 10.7554/eLife.53111 |
| Citation | Sampson TR, et al. (2020) A gut bacterial amyloid promotes alpha-synuclein aggregation and motor impairment in mice. Elife 9:e53111 |
| abstractText | 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 (alphaSyn), we reveal that colonization with curli-producing Escherichia coli promotes alphaSyn pathology in the gut and the brain. Curli expression is required for E. coli to exacerbate alphaSyn-induced behavioral deficits, including intestinal and motor impairments. Purified curli subunits accelerate alphaSyn 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 alphaSyn aggregation and disease in the gut and the brain. |
