Mécanismes moléculaires et cellulaires régulant la présentation antigénique mitochondriale dans le cadre des maladies neurodégénératives

 

Diana Matheoud

Centre hospitalier de l'Université de Montréal [CHUM]

 

Domaine : neurosciences, santé mentale et toxicomanies

Programme Chercheurs-boursiers - Junior 1

Concours 2019-2020

Neurodegenerative diseases such as Parkinson's disease, multiple sclerosis or amyotrophic lateral sclerosis are linked to dysfunctions of the mitochondria, the organelle responsible for energy production in the cell. It has also been shown that the immune system is partly responsible for these diseases. However, until now there has been no link between the immune system and mitochondrial dysfunction. We have recently demonstrated that a new mitochondrial antigen presentation (MitAP) pathway is a link between mitochondrial dysfunction and immune system activation. Indeed, this pathway is regulated by two proteins, encoded by two genes linked to Parkinson's disease, PINK1 and Parkin, which have not only a role in mitochondrial homeostasis but also in the immune system, making for the first time the link between these two components of the disease.

My research project aims to elucidate the role of MitAP in neurodegenerative diseases and in particular to look for the consequences of such a response in patients with an autoimmune response to mitochondrial self-antigens. Moreover, I am looking for molecular partners that could play a role in the MitAP antigen presentation pathway and that could therefore represent potential therapeutic targets. In addition, my project aims to understand how mitochondrial antigens are tolerated by the body; in other words, how mitochondria, which is an organelle of bacterial origin, is not recognized as a foreign organism by the body and does not trigger autoimmune responses under normal conditions. The concept of MitAP can profoundly alter our vision of Parkinson's disease and other neurodegenerative diseases, as the introduction of an autoimmune component would affect therapeutic approaches for the management of these diseases.