Multiomic Analysis Reveals Molecular Pathways Associated with Intestinal Aggregation of α-Synuclein.

ABSTRACT: Aggregates of the protein α-synuclein may initially form in the gut before propagating to the brain in Parkinson's disease (PD). Indeed, our prior work supports that enteroendocrine cells, specialized intestinal epithelial cells, could play a key role in the development of this disease. Enteroendocrine cells natively express α-synuclein and form synapses with enteric neurons as well as the vagus nerve. Severing the vagus nerve reduces the load of α-synuclein aggregates in the brain, suggesting that this nerve is a conduit for gut-to-brain spread. Enteroendocrine cells line the gut lumen; as such, they are in constant contact with metabolites of the gut microbiota. We previously found that when enteroendocrine cells are exposed to nitrite─a potent oxidant produced by gut bacterial Entero

SUBMITTER: Balsamo JM 

PROVIDER: S-EPMC12813975 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature