De Miranda Lab

Gene-environment interactions in Parkinson’s disease and neurodegeneration

Research

Our lab studies the effects of environmental toxicants in the risk for Parkinson’s disease and related neurodegenerative conditions.

Our ultimate goal is to understand the pathology that drives selective toxicity of dopaminergic neurons to certain environmental contaminants, such as pesticides and organic solvents. By uncovering these mechanisms, we may better predict Parkinson’s disease risk, improve treatments, and work to mitigate environmental exposures with the most negative impact.

Highlighted Publications

Trichloroethylene, a ubiquitous environmental contaminant in the risk for Parkinson’s disease

Sex differences in rotenone sensitivity reflect the male-to-female ratio in human Parkinson’s disease incidence

Astrocyte-specific DJ-1 overexpression protects against rotenone-induced neurotoxicity in a rat model of Parkinson’s disease

Gene-Environment Interaction in
Parkinson’s disease

Parkinson’s disease etiology exists on a spectrum. Some Parkinson’s disease cases appear to be purely inherited (genetic), and others are likely a result of direct chemical or pathogen exposure (environment). Most (approximately 85%) are a result of gene-environment interaction. The type of exposure or underlying vulnerability might also drive disease phenotype.

Organic Solvents

Organic solvents are a type of industrial byproduct implicated in neurotoxicity.  Solvents may be used in factories, chemical production sites, dry cleaners, or sold for commercial use. Some organic solvents, such as the chlorinated solvent trichloroethylene (TCE), are associated with increased Parkinson’s disease risk, particularly for those who live in areas of high contamination.

The map at the right shows the location and estimated amount of all chlorinated solvents and toluene that were released into the environment in 1987. Many of these compounds are still in the environment today.

Data: Toxics Release Inventory (TRI) US EPA. Map generated with Tableau.

 

Pesticides

Many pesticides have been linked to Parkinson’s disease risk, from the historical use of Agent Orange (DDT) to the organic pesticide rotenone. Paraquat is a widely applicated herbicide currently used in the United States. Individuals exposed to paraquat have approximately 2-3x greater risk of developing Parkinson’s disease.

The map to the left is courtsey of the US Geological Survey (USGS). Explore more about pesticide use in the US on the USGS website.

Common Mechanisms of Neurotoxicity

To better understand how certain environmental contaminants increase risk for Parkinson’s disease, the De Miranda Lab is currently studying common mechanisms of dopaminergic toxicity between pesticides and organic solvents. For example, mitochondrial dysfunction caused by the pesticides rotenone and paraquat, and the solvent TCE, is likely a convergence point of toxicity in dopaminergic neurons.