Aperçu du projet

Parkinson’s disease (PD) is a common brain disorder that gradually affects movement, balance, and coordination. It mainly results from the loss of nerve cells that produce dopamine, a chemical that helps control motion. Although inflammation in the brain has long been observed in people with PD, scientists still do not fully understand what triggers it or how it contributes to nerve cell death.

Our research explores a new idea that could transform the way PD is understood and treated. We propose that PD may have components of an autoimmune disease—one in which the body’s own immune system mistakenly attacks its neurons. More specifically, we think this attack targets mitochondria (powerhouses inside cells that generate energy) that are presented to immune cells at the neurons surface. In this scenario, certain immune cells known as cytotoxic T cells would recognize parts of mitochondria as foreign and destroy the neurons that contain them.

Recent findings support this possibility. In both cell and animal models, when a mitochondrial protein called PINK1 is missing or malfunctioning—a known genetic cause of PD—the immune system can become activated against mitochondrial components. This process, called mitochondrial antigen presentation (MitAP), can lead to the generation of harmful T cells that damage neurons. In our preliminary work, we found that in people with PD, T cells react strongly to a mitochondrial protein named PDH-E2, producing inflammatory molecules typical of autoimmune reactions. We also observed that human dopamine-producing neurons can display PDH-E2 fragments on their surface under stress, effectively marking themselves for attack.

By uncovering this hidden connection between mitochondria and the immune system, our project aims to reveal a new biological pathway driving PD. Ultimately, this could open the door to immune-targeted therapies capable of preventing or slowing the loss of dopaminergic neurons.

Chef d'équipe

Jo Anne Stratton , Montreal Neurological Institute, McGill University

Membres de l'équipe

Julian Hercun, Université de Montréal

Diana Matheoud, CEO SENSYRA

Tom Durcan, McGill University

Partenaire et Donateurs

Krembil Foundation