Grant: International COEN Initiative in Neurodegeneration

The exact cause of Parkinson's disease (PD) remains unknown and there is currently no cure for the disease. This is why there is a critical need for clinically-relevant biomarkers new therapeutic avenues. In this project, we will explore new research aspects of PD and atypical parkinsonism, related to autoimmunity (the immune attack of the self) triggered by flaviviruses. Indeed, these types of viruses are endemic in regions where atypical parkinsonism is highly frequent (such as Guadeloupe and Martinique) and are particularly associated with Parkinsonian features. Moreover, flavivirus infection is also associated with major mitochondrial disorders. Mitochondria was originally described as the powerhouse of the cell. However, the recent discoveries have highlighted the major role of this organelle in the regulation of the immune response. Particularly, our team have recently shown that the presentation of the proteins from the mitochondria leads to autoimmunity and to PD in a murine model. Therefore, we hypothesize that flavivirus infection trigger autoimmune attacks of dopaminergic neurons (target neurons in PD) through the induction of mitochondrial antigen presentation. Not only this would greatly impact the scientific community because of the first evidence of autoimmunity in PD and atypical parkinsonism patients, but it would generate several promising biomarkers.