Does flavivirus infection trigger mitochondrial antigen presentation and autoreactive Tcell response in parkinsonism?

Annie Lannuzel (France), Michel Panisset (Canada)

Although, Parkinson’s disease (PD) is a common neurodegenerative disorder, the exact cause remains unknown and there is currently no cure. As for, there is a critical need for clinically-relevant biomarkers and new therapeutic avenues. In this project, we will explore new approaches to PD and atypical parkinsonism research, related to autoimmunity (the immune attack of the self) triggered by flaviviruses. Indeed, flaviviruses 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, recent discoveries have described an important role in the regulation of immune responses. Particularly, our team has recently shown that major histocompatibility complex presentation of peptides derived from mitochondrial proteins leads to autoimmunity and PD phenotypes in mouse model of infection. Therefore, we hypothesize that flavivirus infection could trigger autoimmune attacks of dopaminergic neurons (target neurons in PD) through the induction of mitochondrial antigen presentation (MitAP). Our findings will not only impact the scientific community because of the first evidence of autoimmunity in PD and atypical parkinsonism patients, but also would generate several promising biomarkers.