Dr. Briana De Miranda: "The Role of Environmental Exposures in Aging and Neurodegeneration"

Environmental exposures are associated with elevated risk for neurodegeneration, including Parkinson’s and Alzheimer’s disease. Despite a clear link to epidemiological risk, the mechanisms underlying neurodegeneration from environmental exposure remain mostly unclear. Beyond both genetics and environment, aging is the most important risk factor for neurodegeneration. In fact, neurodegeneration is hypothesized to be essentially an accelerated aging phenotype, thus, our research seeks to understand how environmental exposures can accelerate aging as a mechanism of disease. Experimental data from our lab shows that exposure to environmental contaminants, such as the organic solvent trichloroethylene (TCE), induces Parkinsonian pathology, including dopaminergic cell death, neuroinflammation, endolysosomal dysfunction, and protein accumulation in the substantia nigra. TCE exposed mice also display cognitive dysfunction and pathology within cognitive brain regions associated with dementia. Within these degenerating brain regions, we also observed significant dysregulation of cell cycle regulating proteins, such as CDK5 and p16Ink4a, which are involved in pathological mechanisms such as tau hyperphosphorylation and senescence. Thus, we suspect that TCE-induced pathology is in part due to cell cycle dysregulation that accelerates aging, which may be a target for therapeutic intervention. Ongoing studies to target these proteins to identify neuroprotection from TCE are underway in our lab.