Study Shows How Agrochemicals Can Increase Risk of Parkinson’s Disease

By Olivia Roscow

29 March 2019

People who are genetically predisposed to Parkinson’s Disease (PD) are at greater risk of developing the disease following exposure to some agrochemicals, and researchers in the Department of Molecular and Cellular Biology have figured out why.

PD is an incurable neurodegenerative condition causing gradual deterioration of movement that affects roughly 1 in 500 Canadians. While the risk of PD typically increases with age, it is now known that exposure to certain agrochemicals increase risk of development of PD in some individuals. Agrochemicals such as rotenone and paraquat negatively affect function of dopamine producing neurons in the brain; degeneration of these neurons is what causes PD in many victims of the disease.

Using stem cells, Prof. Scott Ryan and his research team investigated the effect of these agrochemicals on neurons and demonstrated that they have significant harmful effects on neurons predisposed to PD, even at levels well below the Environmental Protection Agency (EPA)’s lowest observed effect level, indicating that such chemicals may be toxic a lower levels than previously believed.

“There isn’t a clear dialogue between agrochemical companies and the research community,” says Ryan, noting both the importance - and difficulty - of finding a balance between human health and agricultural needs.

Neurons are one of the main types of cell that make up the brain. In order to provide the energy needed for signals to travel throughout the brain, neurons need to traffic organelles called mitochondria between different parts of a neuron. The travel of mitochondria is dependent on “motor proteins” that attach the mitochondria to the cytoskeleton, the cell’s structural filaments which also transport organelles within the cell.  In this carefully constructed transportation system, motor proteins are like vehicles while the cytoskeleton is the highway they travel along.

But the Ryan lab found that some agrochemicals can chemically modify the filaments of the cytoskeleton, making it difficult for motor proteins to grab on to.   This impaired mitochondrial transport is one of the reasons that PD neurons are under more stress than healthy neurons.

In healthy neurons, exposure to agrochemicals alone is not enough to trigger PD.  However, in people with a mutation that predisposes them to the mitochondrial stress, a low level exposure to agrochemicals is sufficient to trigger chemical alterations of the cytoskeleton. This means that in those individuals with a mutation, exposure to agrochemicals significantly increases their risk of developing PD.

“The baseline level of stress is higher in people with this genetic mutation,” notes Ryan. “It becomes easier for them surpass the threshold to develop PD and thus they are at a higher risk than other people.”

Given the prevalence of agrochemicals, particularly in rural environments, and the degree of cellular dysfunction they can cause, the study raises serious questions about how these compounds are regulated and used.

“There is no perfect chemical replacement for harmful agrochemicals.  However, risks can still be minimized by finding alternatives.”

But according to Ryan, knowing how agrochemicals can cause PD also means there may be a way to help mitigate the disease with drugs. He and his team found that the effects of PD in neurons in the lab could be reversed by treatment with a compound that inhibited the effect of agrochemicals on the cytoskeleton. Unfortunately, the compound in question would likely cause adverse side effects in PD patients. Further research in the Ryan lab will look into other candidate compounds that can deliver the same result, without causing detrimental effects on other processes in the human body.

Read the full story in the FASEB Journal.

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