By Roberta Attanasio, IEAM Blog Editor
For the past few years, Parkinson’s disease and its association with exposure to pesticides has been the topic of a hot debate – one after the other, studies have shown a clear epidemiologic link between disease development and pesticide exposure without, however, identifying any related mechanism of action. Finally, in January 2013, results published in the journal Proceedings of the National Academy of Sciences pointed out a mechanism of action for the fungicide benomyl, a persistent pesticide that is still present in the environment despite having been banned by the U.S. in 2001. Now, results from a new study published in the current issue (February 4, 2014) of the journal Neurology show that several additional pesticides may be involved in the development of Parkinson’s disease, with a mechanism similar to that described for benomyl.
Parkinson’s disease is a chronic and progressive neurodegenerative disorder that affects nearly one million individuals in the U.S. According to the Parkinson’s Disease Foundation, tell-tale symptoms are tremor of the hands, arms, legs, jaw and face, slowness of movement, stiffness of the limbs and trunk as well as impaired balance and coordination. The disease is primarily caused by the death of neurons located in a specific area of the brain – the substantia nigra. Some of these neurons produce dopamine, a messenger molecule involved in the control of movement and coordination. In individuals with Parkinson’s disease, the decrease in dopamine production caused by neuron death leads to impaired movement and coordination.
As shown in the 2013 study, the fungicide benomyl inhibits aldehyde dehydrogenase (ALDH) – an enzyme that converts aldehydes to less toxic compounds. Aldehydes are highly toxic to neurons that produce dopamine and, therefore, by inhibiting ALDH, benomyl leads to neuron damage.
In the new population-based, case-control, epidemiologic study, the researchers used a test that they developed to identify pesticides able to inhibit the activity of ALDH. They found that several of these pesticides experimentally inhibited ALDH activity in neuronal suspensions, and exposures to these same pesticides were associated with 2- to 6-fold increases in the risk of developing Parkinson’s disease in a human population. These pesticides fell into four classes – dithiocarbamate, imidazole, dicarboxymide, and organochlorine. For all the ALDH-inhibiting pesticides identified in the study, the risk of developing disease increased according to increasing levels of exposure. In addition, the researchers found that the risk of developing disease increased in individuals that are not only exposed to the pesticides, but also possess a genetic variant of the ALDH gene. Interestingly, the association between Parkinson’s disease and genetic variants was observed only when an environmental contribution was also considered.
The study shows that inhibition of ALDH may be an important mechanism contributing to the development of Parkinson’s disease and identifies pesticides that should be avoided to reduce the risk of developing the disorder (these pesticides are clearly listed in the published paper). In addition, the study opens up an intriguing possibility for Parkinson’s patients – that of a potential cure. By eliminating toxic aldehydes or increasing the activity of ALDH, it might be possible to slow or reverse disease progression, and this may be true especially for patients that develop Parkinson’s disease in association with exposure to pesticides.