A gut bacterial amyloid promotes α-synuclein aggregation and motor impairment in mice

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.

Challis, CollinCalifornia Institute of Technology (Caltech) (författare)
Jain, NehaUniversity of Michigan (författare)
Moiseyenko, AnastasiyaCalifornia Institute of Technology (Caltech) (författare)
Ladinsky, Mark S.California Institute of Technology (Caltech) (författare)
Shastri, Gauri GCalifornia Institute of Technology (Caltech) (författare)
Thron, TarenCalifornia Institute of Technology (Caltech) (författare)
Needham, Brittany D.California Institute of Technology (Caltech) (författare)
Horvath, Istvan,1979Chalmers tekniska högskola,Chalmers University of Technology(Swepub:cth)istvanh (författare)
Debelius, Justine WUniversity of California (författare)
Janssen, StefanUniversity of California (författare)
Knight, RobUniversity of California (författare)
Wittung Stafshede, Pernilla,1968Chalmers tekniska högskola,Chalmers University of Technology(Swepub:cth)perwit (författare)
Gradinaru, VivianaCalifornia Institute of Technology (Caltech) (författare)
Chapman, MatthewUniversity of Michigan (författare)
Mazmanian, Sarkis KCalifornia Institute of Technology (Caltech) (författare)
California Institute of Technology (Caltech)University of Michigan (creator_code:org_t)

Av författaren/redakt...: Sampson, Timothy ...; Challis, Collin; Jain, Neha; Moiseyenko, Anas ...; Ladinsky, Mark S ...; Shastri, Gauri G; visa fler...; Thron, Taren; Needham, Brittan ...; Horvath, Istvan, ...; Debelius, Justin ...; Janssen, Stefan; Knight, Rob; Wittung Stafshed ...; Gradinaru, Vivia ...; Chapman, Matthew; Mazmanian, Sarki ...; visa färre...

Om ämnet

MEDICIN OCH HÄLSOVETENSKAP: MEDICIN OCH HÄLS ...; och Medicinsk biotek ...; och Medicinsk biotek ...

MEDICIN OCH HÄLSOVETENSKAP: MEDICIN OCH HÄLS ...; och Medicinska och f ...; och Mikrobiologi ino ...

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.