Briana De Miranda, Ph.D.,
Photography: Jennifer Alsabrook-TurnerThe United States Department of Defense has awarded more than $700,000 to researchers at the University of Alabama at Birmingham to study how exposure to trichloroethylene, or TCE, affects neurodegeneration and cognitive dysfunction in Parkinson’s disease. The grant is part of the DoD’s Toxin Exposure Research Program.
While 85 percent of parkinsonism has no genetic cause, TCE is a known environmental factor associated with elevated Parkinson’s disease risk. It is a common ingredient in refrigerants and degreasing compounds and is used as a chemical feedstock. The application of TCE in industrial and military settings has resulted in widespread occupational exposure and environmental contamination.
One of the most significant TCE exposure events occurred between the 1950s and 1980s where high levels of TCE were found in the soil and groundwater at the U.S. Marines base at Camp Lejeune, North Carolina. As a result, individuals who lived and worked at Camp Lejeune are at an elevated risk for several diseases, including cancer, autoimmune disease and Parkinson’s disease.
“Despite TCE’s being a known Parkinson’s disease risk factor, we understand very little about the mechanisms by which TCE causes neurodegeneration and cognitive impairment,” said Briana De Miranda, Ph.D., assistant professor in the UAB Center for Neurodegeneration and Experimental Therapeutics in the Marnix E. Heersink School of Medicine. “Our study will evaluate whether T cell activation caused by TCE exposure influences inflammation in the brain and leads to neuropathology and cognitive decline.”
T cells, immune cells that monitor and respond to internal and external stimuli, play a role in the inflammatory response caused by accumulation of the protein alpha-synuclein. This protein, when accumulated, forms Lewy bodies which are a hallmark brain pathology in Parkinson’s disease and dementia with Lewy bodies. Studies have also shown that individuals with more activated T cells within their blood had worse cognition, suggesting that dysregulated T cells are involved with cognitive decline.
De Miranda’s study will also evaluate whether T cell inhibitors already approved by the Food and Drug Administration are protective against T cell activation, neurodegeneration and cognitive decline caused by TCE in exposed mice.
“The study is designed to benefit all individuals who spontaneously develop Parkinson’s disease but has a particular relevance for those who served in the military or lived on military bases,” De Miranda said. “Our goal is to uncover how environmental exposures influence Parkinson’s disease so that we can provide new treatment options to slow or stop symptoms such as cognitive decline across the Parkinson’s spectrum.”