Story adapted from its original feature on Researchfeatures.com: https://researchfeatures.com/2018/04/05/agricultural-toxins-parkinsons-disease/
Widely used in agriculture, Paraquat is a powerful herbicide that provides fast and effective results for ridding farms and gardens of weeds. This controversial chemical was banned in 2007 by the European Union and is classified as “restricted use” in the U.S. Recent studies suggest that chronic exposure to this weedkiller could damage brain cells and may even lead to a higher risk of Parkinson’s disease (PD). Current studies by Byron Jones, PhD, professor in the Department of Genetics, Genomics and Informatics at UTHSC suggest that susceptibility to paraquat-related PD may be related to host genetics. His research further looks at how genes decide who is more at risk to paraquat’s neurotoxic effects.
Parkinson’s disease is a neurodegenerative disease which causes a loss of motor control and progressive cognitive decline in patients. This incurable disease is categorized as familial or sporadic, with sporadic being the most commonly diagnosed. In cases of sporadic PD, the cause is typically unclear andthe complexity high as it involves multiple genes. Factors such as environment and lifestyle play a role in sporadic diseases, and mounting evidence indicates a correlation between agricultural workers with chronic exposure to toxic herbicides and a heightened risk of developing sporadic PD.
The direct links between paraquat to the cause of Parkinson’s disease are unclear, however, with conflicting information found in both public health and animal model literature. Dr. Jones speculates that some of these discrepancies are not due to a lack of relationship but to heterogeneity in the people and animals studied, making the data hard to interpret because they fail to account for individual differences. Looking to identify the genetic risk factors that might modify susceptibility, Dr. Jones hypothesizes that some individuals exposed to paraquat could be at a greater risk of developing PD even if their living and working conditions are the same as others. His recent award from the National Institute of Environmental Health Sciences for $2.6 million will support a five-year project researching susceptibility and the mechanism of neurotoxicity using genetically well-defined mouse models.
One recent study examining the neurological effect of paraquat found different amounts of dopaminergic neurons affected by the toxin despite the two mice strains used having equivalent amounts of the herbicide in the midbrain. These findings underline the significant role genetics play on one’s susceptibility to paraquat’s effects, enabling investigators to “reverse” study the genes and biochemical pathways that could be regulating this. If a “toxic-sensitive genotype” is discovered, it will play a crucial role in determining individuals who might be at an increased risk of PD due to paraquat exposure and could provide new safety information for agricultural workers.
Additional research into the specific mechanism through which paraquat could cause Parkinson’s disease are being investigated, too. Current thinking suggests the toxin is associated with an increased production of harmful reactive oxygen species or free radicals, leading to dysfunction and death of dopamine neurons linked to the onset of Parkinson’s disease. Dr. Jones’ lab is specifically looking into iron regulation in the substantia nigra which has been shown to be disrupted after paraquat exposure and mysteriously alter gene expression of iron ion-binding proteins in more vulnerable mice. They hypothesize that faulty iron regulation in the brains of susceptible animals (and humans) could cause an influx of free iron into the midbrain producing oxidative damage to dopaminergic neurons, leading to PD. Further damage may occur due to dysfunction of mitochondria, a notable happening in susceptible mice. These fundamental, energy-generating parts of the cell have been associated with pathophysiological dysfunction of Parkinson’s disease for years. While there is still a lot to be discovered, Dr. Jones’ lab aims to show that genetics could play a key role in determining one’s susceptibility to Parkinson’s disease and discover the potential mechanisms linking paraquat to brain damage. Discoveries made by Dr. Jones could eventually help determine genetic vulnerability in workers exposed to agricultural toxins.