A gut bacterial amyloid promotes α-synuclein aggregation and motor impairment in mice
Artikel i vetenskaplig tidskrift, 2020

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.

neuroscience

Curli

mouse

infectious disease

E. coli

microbiome

microbiology

alpha-synuclein

Författare

Timothy R. Sampson

California Institute of Technology (Caltech)

Collin Challis

California Institute of Technology (Caltech)

Neha Jain

University of Michigan

Anastasiya Moiseyenko

California Institute of Technology (Caltech)

Mark S. Ladinsky

California Institute of Technology (Caltech)

Gauri G Shastri

California Institute of Technology (Caltech)

Taren Thron

California Institute of Technology (Caltech)

Brittany D. Needham

California Institute of Technology (Caltech)

Istvan Horvath

Chalmers, Biologi och bioteknik, Kemisk biologi

Justine W Debelius

University of California

Stefan Janssen

University of California

Rob Knight

Department of Computer Science and Engineering

University of California

Pernilla Wittung Stafshede

Chalmers, Biologi och bioteknik, Kemisk biologi

Viviana Gradinaru

California Institute of Technology (Caltech)

Matthew Chapman

University of Michigan

Sarkis K Mazmanian

California Institute of Technology (Caltech)

eLife

2050-084X (ISSN)

Vol. 9

Ämneskategorier

Biokemi och molekylärbiologi

Medicinsk bioteknologi (med inriktning mot cellbiologi (inklusive stamcellsbiologi), molekylärbiologi, mikrobiologi, biokemi eller biofarmaci)

Mikrobiologi inom det medicinska området

DOI

10.7554/eLife.53111

PubMed

32043464

Mer information

Senast uppdaterat

2020-04-16