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.