"The Enteric Nervous System in gut and brain disorders" 

Parkinson's disease can be considered the prototypical neurodegenerative disease of the gut-brain axis. Indeed, lesions similar to those observed in the central nervous system (alpha-synuclein deposits) are present in the enteric nervous system in the vast majority of people with Parkinson's disease, and digestive disorders (constipation, gastric fullness, etc.) are common during the course of the disease. It is proposed that the digestive tract and the enteric nervous system play a role in the initiation and development of the disease. Our team was the first to show that it was possible to detect alpha-synuclein deposits in enteric neurons from a simple digestive biopsy opening the way to a histopathological diagnosis of the disease during the patient's lifetime. We later showed that the lesion load of alpha-synuclein in digestive biopsies was related to the severity of Parkinson's disease. Our current project aims to better understand the digestive damage during the disease by focusing not only on enteric neurons but also on enteric glial cells and intestinal epithelial cells. The IBIMPark project (Laurène Leclair, principal investigator) studies inflammation and digestive permeability in early Parkinson's disease using digestive biopsies. Sébastien Paillusson is studying the physiological role of endoplasmic reticulum membranes associated with mitochondria in enteric neurons and their possible role in the enteric neuropathy of Parkinson's disease. Our third project focuses on the regulation of the expression in enteric neurons and glia of the LRRK2 protein that is involved in familial forms of Parkinson's disease.