Denis Soulet
Laval University, Canada
Title: Estrogen based hormonal therapy to modulate the intestinal innate immune response in Parkinson’s disease
Biography
Biography: Denis Soulet
Abstract
Parkinson’s disease (PD) is a neurological disorder characterized by motor symptoms which are often preceded by non-motor symptoms, including gastrointestinal dysfunctions. Common treatments are only symptomatic; there is still no disease modifying drug available to cure patients. Since numerous pro-inflammatory markers have been measured in the central and peripheral nervous system, this deleterious immune response seems to be a potential target to develop new therapeutic strategies. Therefore, a better understanding of the role of the immune response in the etiology and progression of PD is essential. During my talk, I will present original data about the impact of the innate immune response on enteric neuronal damage in PD models. At first, we characterized the immune response induced by the neurotoxin MPTP in the enteric nervous system of partially immunodeficient mice. We demonstrated the timeline of inflammatory events occurring prior to the neuronal demise and the critical role of monocytes and macrophages in the gut. Thereafter, we tested various estrogenic compounds for their immunomodulatory and neuroprotective properties in PD models both in vivo and in vitro, delineating the major contribution of various estrogenic receptors, mainly the G Protein-coupled Estrogen Receptor 1 (GPER1). More recently, we successfully explored the therapeutic potential of a clinically approved selective estrogen receptor modulator, Raloxifene, for drug repurposing in PD. In conclusion, our data highlight the critical role of the immune response at early stages of PD and the immunomodulatory and neuroprotective potential of estrogen-based hormonotherapy at the pre-clinical level.
