Fig. 2.

Inflammation and cross-seeding: two hypotheses of abnormal aggregated protein ccumulation involving the gut. The left panel shows the “cross-seeding” hypothesis. Aggregated proteins (especially α-syn) produced in the gut propagate in a prion-like manner through the vagus nerve to the brainstem. Bacterial amyloid (e.g., curli) promote abnormal protein aggregation through cross-seeding. The right panel shows the “inflammation” hypothesis. Dysbiosis of gut microbiota activate the innate immune system and increase the production of proinflammatory cytokines and induce inflammation in the brain via systemic circulation.