Grant: Project Grant

Parkinson's disease (PD) is characterized by motor impairment associated with the loss of dopaminergic neurones (DNs). Recent evidences indicate that the disease might be initiated away from the brain in peripheral tissues and involve autoimmune mechanisms. We have shown that two proteins associated with PD, PINK1 and Parkin, actively repress the immune system by limiting the presentation of mitochondrial antigens. In the absence of these proteins, or during a loss of function, stress conditions related to inflammation and fever triggers the presentation of mitochondrial proteins at the surface of a variety of cells of the immune system, as well as DNs. Our data indicate that this process engages autoimmune mechanisms leading the the establishment of cytotoxic CD8+ T cells able to recognize and attack DNs. In the next 5 years, we will characterize the role of PD-related proteins in mitochondrial antigen presentation (MitAP) and the engagement of autoimmune mechanisms. Understanding the molecular mechanisms regulating MitAP is of prime importance to develop therapies that would target the immune system.