Briana De Miranda, Ph.D., associate professor in the UAB Department of Neurology, is leading NIH-funded research examining how environmental exposures may contribute to Parkinson’s disease.
Once thought to be predominantly genetic, Parkinson’s disease is increasingly linked to environmental exposures such as pesticides, solvents, heavy metals, and air pollution. However, research on environmental risks for Parkinson’s has traditionally been difficult to conduct, as experimental systems poorly replicate the complex exposures encountered in human populations worldwide.
An award from the National Institute of Environmental Health Sciences, part of the NIH, is helping De Miranda address this. The Outstanding New Environmental Scientist (ONES) Award supports De Miranda’s project, “The role of lysosomal impairment in trichloroethylene‑induced Parkinsonian neurodegeneration,” with approximately $2.2 million in total funding.
“The ONES award is a transformative program to provide my lab the ability to study environmental risks for Parkinson’s using innovative and in-depth tools that would be difficult to attain with more traditional funding mechanisms,” De Miranda said.
Parkinson’s disease is a progressive neurodegenerative disorder marked by movement‑related symptoms and the buildup of misfolded proteins in the brain. While some cases are linked to inherited genetic risk factors, most are believed to develop through a combination of genetic susceptibility and environmental exposure.
De Miranda’s research focuses on understanding how environmental contaminants may contribute to Parkinson’s disease risk. Her work centers on trichloroethylene, or TCE, a chlorinated organic solvent that has been widely used in industrial settings and remains a common environmental contaminant. Exposure to TCE has been linked to an increased risk of Parkinson’s disease, though the underlying biological mechanisms are not yet fully understood.
“TCE is a widespread volatile organic contaminant with a clear link to Parkinson’s,” De Miranda said. “The ONES award has provided us with the ability to build an inhalation system to better replicate how humans are exposed to the solvent, and therefore, we can better understand how it kills neurons and creates Parkinson’s pathology in the brain.”
Using environmentally relevant inhalation models, the team has examined how TCE exposure affects protein accumulation and the health of dopamine‑producing neurons in the brain. The research also explores the role of LRRK2, a Parkinson’s disease–associated kinase, to better understand how genetic and environmental factors may converge on lysosomal dysfunction, a key cellular process involved in clearing damaged proteins.
Progress from the De Miranda lab at UAB has already shown that inhalation exposure to TCE causes more pronounced dopamine neuron loss than ingestion through drinking water. These findings provide an important missing link in understanding risk for Parkinson’s from TCE exposure and allow De Miranda to uncover the mechanisms driving neurodegeneration from solvent inhalation.
“The ultimate goals of this study are to understand the molecular mechanisms by which TCE triggers and facilitates Parkinson’s neurodegeneration,” De Miranda said. “We hope to identify disease prevention methods as well as potential pathways for therapeutic intervention that could benefit all people with Parkinson’s.”