Oxidative stress-induced Nrf2 misfolding in Parkinson’s disease

Oxidative stress and aging are the primary risk factors for Parkinson’s disease (PD). The protein Nrf2 is particularly important in fighting oxidation and the associated damage in the brain as it activates antioxidant enzymes. Nrf2 is regulated by another protein called Keap1. These two proteins can get damaged under excessive oxidative stress conditions and thus contribute to neuronal death. In my study I will delve into how exactly Nrf2/Keap1 malfunction contributes to PD. I will study the different expression levels, localization, and activation of Nrf2/Keap1 in brain samples of PD patients using biochemical approaches and microscopy. Furthermore, by using well-established PD cell models co-expressing Nrf2/Keap1 with the PD-associated protein a-synuclein, we will study their interactions in PD. Cannabidiol (CBD), one of the main non-psychoactive molecules of Cannabis sativa, is a strong antioxidant that may mitigate the damage to Nrf2/Keap1, activate the Nrf2 pathway and thus slow down or even prevent neurodegeneration in PD. In sum, our study will elucidate the Nrf2 and Keap1 pathway in PD and assess CBD as a potential therapeutic for PD.

Faculty Supervisor:

Martin Duennwald

Student:

Partner:

Parkinson Society Southwestern Ontario

Discipline:

Life Sciences

Sector:

Other services (except public administration)

University:

The University of Western Ontario

Program: