DJ-1 function and oxidative stress (Inter-lab project)

National Institute On Aging

Investigators

Linked publications & trials

Abstract

We have been interested in the relationship between oxidative stress and DJ-1, a rare cause of recessive Parkinson's disease, for several years and have focussed the relationship between oxidative stress and mitochondrial localization. In the current period, we have explored the effects of DJ-1 deficiency in the brains of mice and rats. We find that loss of DJ-1 alters cellular signaling pathways that result, at a cellular level, in the accumulation of changes in metabolic enyzmes. To follow up on these observations, we have collaborated to produce two new animal models of PD. First, we have crossed DJ-1 knockout mice with animals that lack the antioxidant gene NQO1. We have now aged those animals and will be performing behavioral analyses and measurements of cell death in the brain. Second, we have generated a new knockout rat model. Published data suggests that there is dopamine neuron occurs in an outbred rat strain lacking DJ-1. Our new model is based on an inbred strain, thus allowing us to minimize genetic background effect. These animals are currently being aged in our facility and will be examined over the next year.