Mitochondrial dysfunction and vulnerability to oxidative stress in induced dopaminergic neurons derived from idiopathic Parkinson’s disease patients
Parkinson’s Disease (PD) is an age-associated movement disorders, mainly caused by the death of dopamine cells in the brain. Over 90% of PD cases are idiopathic (iPD), that is, of unknown etiology. What causes dopamine cell death is not fully understood, but evidence suggests that mitochondria, the powerhouse of the cell, is more vulnerable to oxidative stress in the PD brain and that defective mitochondria are not properly recycled, further creating damages to the dopamine cells. Given the lack of system that can model the effects of age on dopamine cells, the changes occurring at the cellular level related to mitochondrial function in the context of PD and aging remain to be elucidated. Recent technological advances, however, have made it possible to obtain dopamine cells from patients that maintain the age of the donor. This characteristic allows to study the impact of factors related to aging on the mitochondrial function. This project aims to study mitochondrial dysfunctions in dopamine cells converted from skin cells of patients with iPD in an environment with high oxidative stress to mimic that found in the PD brain. This will provide insight into the contribution of mitochondrial defects to the development of idiopathic PD and how this can be used as a therapeutic target in drug development, as well as to refine patient selection for clinical trials and personalized medicine.
Emilie Legault , Université de Montréal
Partners and Donors
Steinberg Foundation and the Growling Beaver Brevet