While commonly attributed to neuronal death in SNpc, postmortem studies have shown α-syn immunoreactivity and LB pathology in
the peripheral, central, and enteric nervous system (ENS).
While the etiology of misfolded α-syn is unknown, various
gut microbiota and substrates are associated with α-syn
dysfunction. Gastrointestinal (GI) dysfunction, a common
feature in the prodromal phase of PD patients, and histological evidence have led to the Braak hypothesis of misfolded α-syn commencement in the ENS and propagation to
brainstem nuclei including the SNpc via the vagus nerve. Altered or stressed gut environment is thought to contribute to
the misfolding of α-syn that subsequently initiates or spurs
its propagation from the gut myenteric plexus. This review
covers clinical and pre-clinical evidence of the involvement
of enteric α-syn in PD related to GI dysfunction and brain
pathology. CLICK TO REVIEW