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New Insight Into How Pesticides May Increase Parkinsonís Risk
- Feb 03 2014
People who were exposed to pesticides that interfere with a key human enzyme showed up to a three-fold increased risk of developing Parkinson’s disease (PD). For those who were more genetically susceptible to Parkinson’s disease, the risk for developing PD increased five-fold. The results appear in the February 4 issue of Neurology.
Many studies have associated exposure to pesticides with an increased risk of PD, but the underlying mechanisms have remained unclear. The study authors, led by Jeff M. Bronstein, M.D., Ph.D., at the University of California, Los Angeles, suspected that an enzyme called ALDH might play a role. ALDH normally helps detoxify dopamine-related substances within cells. The researchers first carried out studies in the lab, exposing neurons to 26 different pesticides and measuring the effect on ALDH.
The scientists also analyzed data from the Parkinson’s Environment and Genes (PEG) Study, including 360 people with PD and 816 healthy individuals who lived in a rural, agricultural area of California. Using a computer model based on state records of pesticide use, they estimated exposures at the participants’ work and home addresses. In addition, they tested the DNA of 354 people with PD and 518 healthy participants for variations in their ALDH gene.
- Eleven of the 26 pesticides tested (all used in farming) inhibited ALDH in neurons studied in the laboratory. Meanwhile 15 of the pesticides, including organophosphates and the pesticide paraquat, did not affect ALDH.
- Exposure to an ALDH-inhibiting pesticide at both the workplace and home was associated with an increased risk of PD. Workplace exposure alone was not associated with an increased risk of PD.
- There was a trend of increasing risk with increasing exposure to multiple pesticides.
- Having a genetic variation in ALDH exacerbated the risk of developing PD if a person was also exposed to pesticides.
- Having the genetic variation in ALDH alone did not make a person more likely to develop PD.
What Does It Mean
Pesticides have been previously shown to increase PD risk. Still, most people exposed to high doses of pesticides do not develop PD. This study supports the generally accepted hypothesis that PD is caused by a combination of genetic and environmental factors by pointing out one possible way that genes and environment may interact to lead to PD.
Specifically, the study showed that having a genetic variation in ALDH exacerbated the risk of developing PD if a person was also exposed to certain pesticides. This theory is scientifically plausible. The enzyme is known to detoxify dopamine-related toxins; therefore, reduced activity of the enzyme, may be linked to PD.
However, further research is needed. For example, since most of the study participants were exposed to more than one of the ALDH-inhibiting pesticides, the study authors could not conclude that any one of them causes PD. Furthermore, they do not yet know how genetic variations may make some people more susceptive. To explore this further, they would need to test cells with the same genetic backgrounds to confirm that ALDH is inhibited. Additionally, the findings should be replicated in other populations to confirm the scientists’ findings that ALDH-inhibiting pesticides are linked to higher risk for PD, and that certain genetic alteration in the ALDH gene may make carriers more susceptible to the effects pesticides.
They also suggest that boosting ALDH enzyme activity or finding alternative ways for cells to neutralize toxins could lead to potential PD therapies for those exposed to pesticides. Further work in the lab will need to explore whether boosting the activity of this enzyme will help people with PD more generally.
The study authors state that ambient exposure to these pesticides should be avoided. It should be noted that the majority of people do not develop the disease due to pesticide exposure, and the exposure the participants likely received was well above what one would encounter from simply eating fruits and vegetables. Those that should be concerned are welcome to contact PDF's HelpLine at (800) 457-6676.
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Source Date: Feb 03 2014