Investigator:
Judit Pallos, PhD
Name of Institution:
Oregon Health and Science University, Portland, OR
Project Title:
Mechanisms of LRRK2-induced neurodegeneration
Investigator Bio:
Dr. Pallos received her PhD from the University of Szeged, Hungary based on work studying Huntington’s disease at the University of California, Irvine. She joined Dr. Ian Martin’s lab at Oregon Health and Science University as a post-doctoral fellow to pursue her interest in the molecular mechanisms of aging and neurodegeneration.
Objective:
To understand the role of neurite branching defects and their mediators in LRRK2-induced dopamine neuron death.
Background:
Degeneration of the axon, the long projection of the nerve cell that extends out from the cell body to communicate with other nerve cells, is observed in both Parkinson’s disease (PD) patients and animal models of the disease. The mechanisms leading to this degeneration and their relationship to death of the neuron are not well understood. Our laboratory recently identified a protein called prospero (PROX1 in mammals) as a modifier of motor deficits and neuronal loss in a mutant LRRK2 fly PD model as well as in primary rodent neurons. Prospero is a transcription factor with an already established role in neuronal outgrowth and maintenance. We seek to identify other proteins that functionally interact with prospero and contribute to neuronal defects.
Methods/Design:
Using the mutant LRRK2 fly across ages, we will measure levels of the cellular targets that prospero is involved in transcribing. We will then utilize a unique single dopamine neuron labeling approach, to determine whether defects in nerve cell projections in the mutant LRRK2 nerve cells can be improved as expression of these targets is altered.
Relevance to Diagnosis/Treatment of Parkinson’s disease:
Understanding the molecular mechanisms that contribute to neurodegeneration can lead to developing new therapeutics for the treatment of PD.