NysnoBio Publishes in Nature Parkinson’s Journal
San Francisco | June 20, 2025 – NysnoBio, with the support of Aligning Science Across Parkinson’s (ASAP) through the Michael J. Fox Foundation for Parkinson’s Research (MJFF), announces publication of studies to understand how PD mutations drive cellular phenotypes. These studies were undertaken because it's still unclear if some PD mutations drive cellular phenotypes more than others.
A comparison of differentiated patient cells from different genetic forms of PD demonstrated that loss of Parkin is a primary driver of dopamine neuron dysfunction. This dysfunction is not present in cortical neurons, demonstrating the specific requirement for Parkin in dopamine neurons.
These graphs clearly demonstrate that normal dopamine neuron function requires the Parkin protein. Without Parkin, dopamine neurons are profoundly impaired, but cortical neurons are not..
Article extract: “Overall, these findings demonstrate cell type specific dysfunctions with different PD mutations that are likely to impact on both selective neuronal vulnerability and the pathologies observed in PD. PRKN lof mutations selectively affected dopamine and not cortical neurons. While PRKN lof dopamine neurons had the expected significant reduction in respiration, they also had reduced lysosomal function (GCase activity) and impaired autophagy, all of which increased the levels of alpha-synuclein puncta. These selective changes were not observed in dopamine neurons from the other PD mutations or in PRKN lof cortical neurons, suggesting these early intrinsic cellular properties in dopamine neurons may drive early-onset PRKN disease.”
Read the full article at Nature.
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