10 pesticides that are neurotoxic and involved in Parkinson's disease
More data suggests a link between exposure to environmental toxins such as pesticides and heavy metals, and the rise of Parkinson's disease.
The link between pesticide exposure and Parkinson's disease
- Studies have shown a link between exposure to chemicals in pesticides and herbicides and the incidence of Parkinson's disease, including the insecticides rotenone and permethrin (commonly used to impregnate clothing or mosquito nets)1.
- A recent study identified 10 pesticides that are directly toxic to dopaminergic neurons.
- In addition, co-exposures (the cocktail effect) result in greater toxicity than each pesticide individually.
A growing threat
CNS disorders are the most common cause of disability worldwide today. The fastest growing of these is Parkinson's disease (PD): the number of people affected doubled to more than 6 million between 1990 and 2015, and is expected to double again to more than 12 million by 2040. Parkinson's is a complex neurodegenerative disease whose etiology is based on genetic susceptibility and environmental factors.2
The search for Parkinson's cause
"For most of human history, Parkinson's was a rare disease. But demographics and by-products of industrialisation have now triggered a Parkinson's pandemic."2 The scientists at the University of Los Angeles (UCLA) included 288 specific substances in a population-based association study and then examined 39 of the epidemiologically suspected pesticides by live cell imaging. In addition, they confirmed the measurements in another cell line to test generalisability in dopamine neurons from different sources.3
Ten pesticides identified, that affect the brain
Ten pesticides caused considerable death of mDA neurons (midbrain dopaminergic neurons) and their neurites. The areas of application and chemical structures of the toxins are very different:
- Propargite (an organosulphite).
- Diquat dibromide (now withdrawn from the market as a contact herbicide and siccative).
- Copper sulphates (still widely used fungicides), for which biologically conclusive links to Parkinson's disease had already been documented in earlier work.
The current study confirmed the previous list, and also identified:
- Dicofol (acaricide).
- Folpet (fungicide).
- Naled (also dibromine, insecticide).
- Endosulfan (insecticide and acaricide, now banned).
- Endothal (herbicide and defoliant), identified as directly toxic to mDA neurons.
In addition, the team studied cardiomyocytes to determine which pesticides are toxic to all cells and not just neurons. Five of the pesticides were shown to be selectively neurotoxic and will be the subject of future tests on other CNS cell types, co-culture systems, and 3D organoids.
They also analysed pesticides typically used in combination in cotton cultivation, and were able to show that co-exposures lead to greater toxicity than any single pesticide. In particular, they found that trifluralin increases toxicity to dopaminergic neurons and leads to mitochondrial dysfunction (dopaminergic neurons are particularly vulnerable in this respect because their energy demand is very high).4
How do we deal with neurotoxic pesticides?
It would be of great relevance to gain more knowledge about what constitutes a clinically relevant dose. The study authors themselves admit that modelling chronic exposure "in the Petri dish" is challenging. They indicate how important it will be to "develop more sensitive assays that can assess phenotypes at low micromolar or nanomolar concentrations. Functional tests, e.g. of neuronal activity, may be more sensitive than testing for apparent toxicity."3
Almost all (8 of the 10) mDA-toxic pesticides remain registered for use with the US Environmental Protection Agency (US EPA). In 2016, about 3 million tonnes of pesticide active ingredients were consumed worldwide, 60% of which were in China. Incidentally, China has the highest number of Parkinson's patients in the world; it is estimated that 5 million people will have the disease in China by 2030.5
Unfortunately, pesticides are not the only substances whose exposure urgently needs to be reduced in order to take momentum out of the rising incidence of diseases. Also becoming increasingly clear is the link to heavy metal exposures, MPTP, and organic pollutants such as PCBs (polychlorinated biphenyls), which have been found in high concentrations in the brains of Parkinson's patients.1
"The proliferation of harmful pesticides that increase Parkinson's risk continues to spread, many people remain undiagnosed and untreated, research funding is stagnant, and the most effective treatment is now half a century old," write four leading neurological experts in the foreword to the book Ending Parkinson's Disease: A Prescription for Action. In it, they go into detail about pesticides, but also how contaminated groundwater and solvents (such as trichloroethylene) spread the disease, the role of head trauma, exercise and diet, and what we can do for those who bear the burden of the disease.
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Can Environmental Toxins Cause Parkinson’s Disease?
- Dorsey, E. R. et al. Global, regional, and national burden of Parkinson’s disease, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016. The Lancet Neurology 17, 939–953 (2018).
- Paul, K. C. et al. A pesticide and iPSC dopaminergic neuron screen identifies and classifies Parkinson-relevant pesticides. Nat Commun 14, 2803 (2023).
- DavidPerlmutterMD. The Alarming Rise in Parkinson’s Disease with Dr. Ray Dorsey | The Empowering Neurologist EP. 167.
- Islam, M. S. et al. Pesticides and Parkinson’s disease: Current and future perspective. Journal of Chemical Neuroanatomy 115, 101966 (2021).
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