Autor: |
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, Pernilla Wittung-Stafshede, Viviana Gradinaru, Matthew Chapman, Sarkis K Mazmanian |
Jazyk: |
angličtina |
Rok vydání: |
2020 |
Předmět: |
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Zdroj: |
eLife, Vol 9 (2020) |
Druh dokumentu: |
article |
ISSN: |
2050-084X |
DOI: |
10.7554/eLife.53111 |
Popis: |
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 α-synuclein (αSyn), we reveal that colonization with curli-producing Escherichia coli promotes αSyn pathology in the gut and the brain. Curli expression is required for E. coli to exacerbate αSyn-induced behavioral deficits, including intestinal and motor impairments. Purified curli subunits accelerate αSyn 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 αSyn aggregation and disease in the gut and the brain. |
Databáze: |
Directory of Open Access Journals |
Externí odkaz: |
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