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A gut bacterial amyloid promotes a-synuclein aggregation and motor impairment in mice
T.R. Sampson, C. Challis, , A. Moiseyenko, M.S. Ladinsky, G.G. Shastri, T. Thron, B.D. Needham, I. Horvath, J.W. DebeliusShow More
Published in eLife Sciences Publications Ltd
PMID: 32043464
Volume: 9
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 (α Syn), we reveal that colonization with curli-producing Escherichia coli promotes α Syn pathology in the gut and the brain. Curli expression is required for E. coli to exacerbate α Syn-induced behavioral deficits, including intestinal and motor impairments. Purified curli subunits accelerate α 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 aSyn aggregation and disease in the gut and the brain. © Sampson et al.
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