Crosstalk Between Alpha-Synuclein and Other Human and Non-Human Amyloidogenic Proteins: Consequences for Amyloid Formation in Parkinson's Disease
Review article, 2020

It was recently shown (Sampson et al., Elife9, 2020) that an amyloidogenic protein, CsgA, present in E. coli biofilms in the gut can trigger Parkinson's disease in mice. This study emphasizes the possible role of the gut microbiome in modulation (and even initiation) of human neurodegenerative disorders, such as Parkinson's disease. As the CsgA protein was found to accelerate alpha-synuclein (the key amyloidogenic protein in Parkinson's disease) amyloid formation in vitro, this result suggests that also other amyloidogenic proteins from gut bacteria, and even from the diet (such as stable allergenic proteins), may be able to affect human protein conformations and thereby modulate amyloid-related diseases. In this review, we summarize what has been reported in terms of in vitro cross-reactivity studies between alpha-synuclein and other amyloidogenic human and non-human proteins. It becomes clear from the limited data that exist that there is a fine line between acceleration and inhibition, but that cross-reactivity is widespread, and it is more common for other proteins (among the studied cases) to accelerate alpha-synuclein amyloid formation than to block it. It is of high importance to expand investigations of cross-reactivity between amyloidogenic proteins to both reveal underlying mechanisms and links between human diseases, as well as to develop new treatments that may be based on an altered gut microbiome.

functional amyloids

food allergens

cross-reactivity

alpha-synuclein

amyloid formation

microbiome

Parkinson’s disease

neurodegeneration

Author

Tony Werner

Chalmers, Biology and Biological Engineering, Chemical Biology

Istvan Horvath

Chalmers, Biology and Biological Engineering, Chemical Biology

Pernilla Wittung Stafshede

Chalmers, Biology and Biological Engineering, Chemical Biology

Journal of Parkinsons Disease

1877-7171 (ISSN) 1877-718X (eISSN)

Vol. 10 3 819-830

Subject Categories

Biochemistry and Molecular Biology

Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)

Microbiology in the medical area

DOI

10.3233/JPD-202085

PubMed

32538869

More information

Latest update

9/3/2020 9