Parkinson’s disease and pesticides – more and more facts

It has been assumed for years that Parkinson’s disease, which is a degenerative disease of a central nervous system arising from dopamine deficiency, may have other causes than genetic ones. It was thought that risk factors may come from external environment as in the case of many other diseases.

A work of Pezzoli and Cereda, which aim was to analyse influence of pesticides and dissolvents on Parkinson’s disease development, was published last year in May in Neurology magazine. In order to make analysis the authors conducted cohort and case-control studies on population. After unification of researched groups they came into conclusion that exposition to any kind of pesticides, herbicides and dissolvents involves higher risk of Parkinson’s disease development. They also stressed that it would be valuable to analyse mechanisms of those correlations.

The challenge was taken up by scientists from University of California in Las Vegas. They wanted to check which pesticides contribute mostly to the disease’s activation and what is the molecular basis of this phenomena. Basing on their previous research they focused on chemicals which inhibit aldehyde dehydrogenase (ALDH) activity in central nervous system. Blockade of this enzyme is a result of 3’,4’-DOPAL depositing in the brain tissue. This correlation is the main precursor of dopamine’s metabolic path and by deposition in central nervous system it leads to neural degeneration. Scientists took neurons from black matter of rat newborns and exposed them to 26 different pesticides. Then they observed reactions. Substances causing enzyme’s inhibition are divided into 4 structural categories. The first of them comprises of dithiocarbamates in which ziram, fungicide containing zinc, have caused 20% inhibition of ALDH activity. Imidazoles- benomyl and triflumizole inhibited 30% and 13% of the activity correspondingly. Dicarboximides – captan and folpet caused 18% and 17% inhibition and dieldrin – synthetic choloroorganic insecticide – 8%. None of the researched organophosphorus compounds, carbamates and triazines did not show such influence.
The scientists also verified variants of ALDH coding gene in order to assess peculiar sensitivity to particular pesticides.

Then they transferred laboratory results on population statistics. 360 people with diagnosed Parkinson’s disease up to the last 3 years were included to research group. 816 healthy people were control group. People from both, researched and control group came from rural regions of California. The participants were analysed by telephone conversation in order to gather demographic information, to assess the risk of exposure to pesticides and to collect information about the place and kind of performed job.

Measurement of exposure to a certain kind of pesticide was done with the use of data from pesticide use reports in California. Then research and control groups were divided into exposed during work and at home. The next division concerned number and type of pesticides. The participants were grouped according to exposure to 3 or more pesticides, exposure to 1 or 2 types of pesticides and non exposed to pesticides inhibiting ALDH activity. The highest risk of Parkinson’s disease development was observed in people who were exposed not only at home, but also at work (65%). In those who were exposed to 3 or more pesticides the risk increased 3 times.

The scientists also proved that coexistence of exposition to ALDH blocking pesticides with certain variant of enzyme’s coding gene increases the risk 6 times.

The discovery of the scientists from University of California allow to conclude that avoiding exposure to pesticides may lower the risk of Parkinson’s disease development. In people who cannot eliminate the risk and who are additionally genetically burdened it would be valuable to introduce pharmacotherapy which would decrease the toxicity of pesticides in the organism.



Written by: Julia Rudnicka, Anna Kozioł

Source:
1. Fitzmaurice AG, Rhodes SL,et al. Aldehyde dehydrogenase variation enhances effect of pesticides associated with Parkinson disease. Neurology. 2014 Feb 4;82(5):419-26.
2. Pezzoli G, Cereda E. Exposure to pesticides or solvents and risk of Parkinson disease. Neurology. 2013 May 28;80(22):2035-41.
3. http://www.medscape.com/viewarticle/820257#2
4. Kozubski W., Liberski P. Neurologia, PZWL 2008.

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