My PD Story

2026 Environmental Trigger Award

Using Toxin Exposures to Find Genes that Protect Neurons from Parkinson’s

In Parkinson’s disease (PD), dopamine neurons in the brain break down over time. This leads to the progressive and worsening symptoms seen in people with PD. However, scientists have observed that some dopamine neurons in the brain are naturally more resilient than others, staying functional while other similar neurons fall apart.

Zachary Freyberg, MD, PhD, a recipient of a Parkinson’s Foundation Environmental Trigger Award, is looking for the genetic reasons why some neurons are more resistant to PD than others. In doing so, he hopes to discover new ways to spread such resilience throughout the brain and protect against the disease.

From his research lab at the University of Pittsburgh, Dr. Freyberg is tackling this question from a highly relevant angle: by observing which dopamine neurons survive following exposure to PD-related toxins. His team has already found two genes in animal models that seem to be associated with neuron resilience: NDUFB1 and ULK1. These genes were more active in neurons that stayed healthy when exposed to pesticides linked to PD. When Dr. Freyberg and his research team turned off those genes, the neurons became vulnerable again, signaling their protective importance.

“By identifying and testing the genes and cellular structures that protect human dopamine neurons, this work may uncover new therapeutic targets and biomarkers for neuroprotection.” – Dr. Freyberg

Now, Dr. Freyberg will determine if NDUFB1 and ULK1 are also important for neuron protection against PD in humans. First, he will grow human dopamine neuron cells in a lab, modifying some samples to overexpress these two genes. After exposing these neurons to PD-related toxins, Dr. Freyberg will observe whether the neurons with more active NDUFB1 and ULK1 resist degeneration better than the unchanged neurons. 

He will also use a technology called cryo-electron tomography to perform microscopic CT scans of the neurons. This will let his team visualize how the biological machinery in the cells like mitochondria are affected by toxins with and without the protection of NDUFB1 and ULK1.

Lastly, Dr. Freyberg will analyze donated brain tissue from people with and without PD to see how NDUFB1 and ULK1 levels associate with healthy and disease-affected neurons. He hypothesizes that they will see higher levels of activity from those genes in the remaining dopamine neurons of PD-affected brains.

If Dr. Freyberg and his team find that NDUFB1 and ULK1 help protect dopamine neurons in humans, this research could open the door for new treatments that fight PD progression. 

“To be chosen and supported by the Parkinson's Foundation is deeply meaningful to me,” said Dr. Freyberg. “This award could lay the groundwork for therapies designed to slow, or even halt, the loss of dopamine neurons that drives Parkinson's disease.”

Meet more Parkinson’s researchers! Explore our My PD Stories featuring PD researchers.