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A gut bacterial amy...
A gut bacterial amyloid promotes α-synuclein aggregation and motor impairment in mice
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- Sampson, Timothy R. (author)
- California Institute of Technology (Caltech)
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- Challis, Collin (author)
- California Institute of Technology (Caltech)
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- Jain, Neha (author)
- University of Michigan
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- Moiseyenko, Anastasiya (author)
- California Institute of Technology (Caltech)
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- Ladinsky, Mark S. (author)
- California Institute of Technology (Caltech)
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- Shastri, Gauri G (author)
- California Institute of Technology (Caltech)
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- Thron, Taren (author)
- California Institute of Technology (Caltech)
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- Needham, Brittany D. (author)
- California Institute of Technology (Caltech)
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- Horvath, Istvan, 1979 (author)
- Chalmers tekniska högskola,Chalmers University of Technology
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- Debelius, Justine W (author)
- University of California
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- Janssen, Stefan (author)
- University of California
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- Knight, Rob (author)
- University of California
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- Wittung Stafshede, Pernilla, 1968 (author)
- Chalmers tekniska högskola,Chalmers University of Technology
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- Gradinaru, Viviana (author)
- California Institute of Technology (Caltech)
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- Chapman, Matthew (author)
- University of Michigan
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- Mazmanian, Sarkis K (author)
- California Institute of Technology (Caltech)
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(creator_code:org_t)
- 2020
- 2020
- English.
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In: eLife. - 2050-084X. ; 9
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https://doi.org/10.7...
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Abstract
Subject headings
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- 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.
Subject headings
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinsk bioteknologi -- Medicinsk bioteknologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Medical Biotechnology -- Medical Biotechnology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Mikrobiologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Microbiology in the medical area (hsv//eng)
Keyword
- neuroscience
- Curli
- mouse
- infectious disease
- E. coli
- microbiome
- microbiology
- alpha-synuclein
Publication and Content Type
- art (subject category)
- ref (subject category)
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- By the author/editor
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Sampson, Timothy ...
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Challis, Collin
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Jain, Neha
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Moiseyenko, Anas ...
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Ladinsky, Mark S ...
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Shastri, Gauri G
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show more...
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Thron, Taren
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Needham, Brittan ...
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Horvath, Istvan, ...
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Debelius, Justin ...
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Janssen, Stefan
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Knight, Rob
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Wittung Stafshed ...
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Gradinaru, Vivia ...
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Chapman, Matthew
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Mazmanian, Sarki ...
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show less...
- About the subject
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Biochemistry and ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Medical Biotechn ...
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and Medical Biotechn ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Microbiology in ...
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eLife
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Chalmers University of Technology
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Karolinska Institutet