Gut power: Modulation of human amyloid formation by amyloidogenic proteins in the gastrointestinal tract

Abstract

Protein assembly into amyloid fibers underlies many neurodegenerative disorders. In Parkinson's disease, amyloid formation of α-synuclein is linked to brain cell death. The gut-brain axis plays a key role in Parkinson's disease, and initial α-synuclein amyloid formation may occur distant from the brain. Because different amyloidogenic proteins can cross-seed, and α-synuclein is expressed outside the brain, amyloids present in the gut (from food products and secreted by microbiota) may modulate α-synuclein amyloid formation via direct interactions. I here describe existing such data that only began to appear in the literature in the last few years. The striking, but limited, data set-spanning from acceleration to inhibition-calls for additional investigations that may unravel disease mechanisms as well as new treatments.

Keywords: Alpha-synuclein; Cross-reactivity; Functional amyloids; Microbiome; Parkinson's disease.