Assay Development for Investigating the Contributions of p75 Neurotrophin Receptor (p75NTR) Signaling to Neurodegeneration Associated with Parkinson’s Disease

The p75 neurotrophin receptor (p75NTR) possesses the ability to promote cell survival or apoptosis upon activation. The specific signaling cascades regulated by p75NTR in neurodegenerative pathologies are poorly understood due to the multifaceted nature of the receptor. Prior studies associate oxidative stress, a cellular condition induced by an overwhelming presence of reactive oxygen species, with promoting proteolysis and subsequent activation of p75NTR in dopaminergic neurons. Dopaminergic neurons express p75NTR and are of interest in neurodegenerative research. The degeneration of these neurons occur during the progression of Parkinson’s Disease. Here, we optimized an in vivo and an in vitro protocol for modeling Parkinson’s Disease. Another aspect of this research was to optimize an automated method to measure the degeneration index (DI) of neurons. Developing an optimized in vivo model of Parkinson’s Disease may provide insight into the role of p75NTR regarding the survival and health of dopaminergic neurons within substantia nigra and striatum regions of the brain. Developing an optimized in vitro model of Parkinson’s Disease may allow for investigation to the effects of p75NTR mediated signaling events associated with oxidative stress on cellular function. The DI is a calculation of neurite degeneration, which allows for the quantification of neurodegenerative diseases. An optimized method of analysis has provided a streamlined approach to calculating the DI and neurite fragmentation in culture. Preliminary data suggests that our optimized protocols serve as a successful model of Parkinson’s Disease and thus allow further analysis into how p75NTR signaling cascades affect cellular outcome in Parkinson’s Disease.