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

National Institute On Aging

Investigators

Linked publications, trials & patents

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. As part of this collaborative project, we have crossed DJ-1 and NQO1 deficient animals, both of which have been shown previously to have protective effects against oxidative damage in parkinsonian-related in vitro or in vivo models. We have a completed large set of behavioral assays in the double homozygote animals and will be examining their brains for any evidence of pathology. We have also made a new strain of DJ-1 knockout rats using CRISPR/Cas9 in the Sprague-Dawley outbred background. After aging these animals, we expect to be able to confirm or refute whether there is spontaneous neurodegeneration.