“A Who's Who of pesticides is therefore of concern to us all. If we are going to live so intimately with these chemicals eating and drinking them, taking them into the very marrow of our bones - we had better know something about their nature and their power.”
― Rachel Carson, Silent Spring

In the nearly sixty years since Rachel Carson first exposed the magnitude of man-made environmental contaminants, entire research fields have been dedicated to understanding human health and disease through the lens of exposure. From this view, we now know the environment (and its role in disease) is not just pesticides applied on our crops or chemicals effused from a factory - it’s the water you drink at home, the food you ate this morning, and the air you breathe as you read this.

By definition, the environment is everything except your inherited DNA. And even that can be influenced from the exposures your parents sustained (i.e. transgenerational epigenetic inheritance). Because of this, all human health and disease is influenced by the environment, without exception. In the case of Parkinson’s disease (PD), the environment takes a more central role; pesticides, industrial byproducts, metals, infections, drug use, head trauma, microbiome, and diet are all implicated in PD pathogenesis. In fact, as approximately 85% of individuals who develop PD are considered idiopathic, Parkinson’s is likely the most environmentally influenced neurodegenerative disease in adults. To this end, incorporating environmental risk into PD research helps advance not only our understanding of the disease, but also in identifying prevention or treatment options.

A (very brief) history of environmental toxicants and PD.

The first environmental contaminants implicated in PD risk were organophosphate pesticides, identified in the 1970s as case studies outlined parkinsonism in individuals directly exposed to these compounds. The 1980s saw the incredible case of a group of young adults who mistakenly self-injected the neurotoxicant MPTP, a contaminant of their intended target, the opioid desmethylprodine. These four people developed immediate and irreversible parkinsonian symptoms, leading to the discovery of MPTP as a highly potent and specific dopaminergic neurotoxicant. The 1990s brought a broader understanding of environmental and occupational risk factors for PD, including pesticides, metals, and well-water use. The last two decades have further uncovered numerous environmental toxicants in the risk for PD, as epidemiological studies described clusters of PD cases as a result of pesticide contamination of agricultural communities (paraquat and maneb), solvent exposure in factories (trichloroethylene), and certain components of air pollution.

Why does PD develop from environmental exposures?

We suspect PD is especially influenced by environmental exposures due to the selective vulnerability of the dopaminergic neurons in the substantia nigra. Dopaminergic neurons are highly active, heavily branched cells that require significant energy demands from the mitochondria. In addition, dopamine itself is a reactive molecule, potentially causing a baseline of oxidative stress these cells must detoxify with a relative paucity of cellular antioxidants. Most (if not all) environmental toxicants that increase PD risk also cause mitochondrial dysfunction or oxidative stress. Therefore, while some neuron populations heal after an exogenous insult, dopaminergic neurons are often irreversibly damaged, and may degenerate as a result of chronic toxicant exposures.

How can we use this information to help individuals with PD?

Parkinson’s is the fastest growing neurological disorder in the world, and is especially increasing in newly industrialized areas. This incidence rate suggests that industrial contaminants are at least partially to blame for the increase in PD, and reducing detrimental environmental exposures could prevent PD onset or delay its progression, as discussed below.

1. Prevent exposure to neurotoxicants: Environmental remediation, filtering systems, and exposure monitoring are all strategies to limit exposure for individuals in contaminated areas. In addition, some countries have banned the use of chemicals associated with PD; for example, the European Union no longer allows the pesticide paraquat to be used for farming. However, most of these chemical regulations are due to the carcinogenicity of a compound. Policy changes made specifically to prevent neurotoxicant exposure implicated in PD would be a major milestone in the fight to end the disease.

2. Identify and protect vulnerable populations: Some individuals are at greater risk for environmental neurotoxicant exposure than others. For example, military service is associated with higher risk for PD than the civilian population, which is likely a result of environmental contaminants (e.g. pesticides, solvents, burn pits) and other factors (e.g. head trauma). Individuals who live with less access to green space, or in underprivileged communities are at a higher burden for exposure than more affluent areas (an environmental justice issue). Locations with high levels of contamination, such as Superfund sites within the United States and other industrial areas, need to be properly remediated prior to developing.

3. Incorporate environmental toxicity into the core of PD research: PD is a complex disease, consisting of both genetic and environmental components. If we better understand the totality of what causes parkinsonian pathology, we can formulate treatments with a higher degree of success in the idiopathic PD population than if each entity is studied in isolation.

Briana R. De Miranda, PhD, is an Assistant Professor at the Center for Neurodegeneration and Experimental Therapeutics, Department of Neurology at University of Alabama at Birmingham. Dr. Miranda will be speaking on the topic of “What’s new from environmental toxins?“ in May at the WPC Virtual Congress.

Ideas and opinions expressed in this post reflect that of the author(s) solely. They do not necessarily reflect the opinions of the World Parkinson Coalition®