The unfolded protein response (UPR) is a life-death switch that instructs aged and overworked cells to self-destruct. We hypothesize that hyper-activation of the UPR is partly responsible for the neuron loss that drives sporadic and inherited forms of Parkinson’s disease (PD), including PD caused by mutations in the gene LRRK2.
We will stain autopsy brain tissue for markers of UPR activation from people with and without PD as well pre-clinical models of the disease. This approach will allow us to conclusively determine if the UPR is over-activated in diseased neurons of PD and therefore a potential target to slow or defeat PD.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
If we find evidence that the UPR is inappropriately activated in PD, we will hasten our efforts to design drugs to turn off this destructive switch and test them in pre-clinical models.
Based on preliminary work by ourselves and others, we expect to see increased UPR activation in PD brain tissue compared to healthy brain tissue. Our approach will allow us to more precisely determine whether UPR activation is restricted to certain cell types or to certain clinical phases of the disease.