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Daily News Blog

30
Jun

Common Fungicide Again Linked to Parkinson’s Disease with Molecular Disruption

(Beyond Pesticides, June 30, 2022) A study by Zhongnan University and Shandong University in China finds that the broad-spectrum fungicide maneb increases Parkinson’s disease (PD) risk and development through alterations in protein and metabolite pathways, resulting in neurotoxicity. Several studies find exposure to chemical toxicants, like pesticides, have neurotoxic effects or exacerbate preexisting chemical damage to the nervous system. Although the mechanism by which pesticides induce disease development remains unclear, this study suggests neurological damage from oxidative stress, cell dysfunction, and synapses impairment, among others, increases the incidence of PD subsequent to pesticide exposure.

Parkinson’s disease is the second most common neurodegenerative disease, with at least one million Americans living with PD and about 50,000 new diagnoses annually. The disease affects 50 percent more men than women, and individuals with PD have a variety of symptoms, including loss of muscle control and trembling, anxiety and depression, constipation and urinary difficulties, dementia, and sleep disturbances. Over time, symptoms intensify, but there is no current cure for this fatal disease. While only 10 to 15 percent of PD cases are genetic, PD is quickly becoming the world’s fastest-growing brain disease. Therefore, research like this highlights the need to examine molecular mechanisms involved in altering chemical processes in the body that cause severe and even fatal health effects. The researchers note that the study reveals “the molecular mechanisms of maneb and other pesticides” that induce PD.

Researchers exposed the human cell line SH-SY5Y to environmentally relevant concentrations of maneb and evaluated mice with the common pathological feature of neurogenerative disease, α-synuclein, in the presence of asparagine endopeptidase (AEP) enzyme activation. Using an in vitro assay, researchers determined cell viability related to dose-dependent maneb exposure at environmentally relevant levels. The results show that α-synuclein mice display PD-like motor impairment behavior after maneb exposure, with proteomics and metabolomics (omics) analyses on mice brain and blood serum constituents indicating alterations in protein and metabolite pathways involved in neurotransmission. To verify the results of the omics studies, researchers used the Western blot analysis and targeted metabolomics, demonstrating maneb induces neurological disturbances related to PD pathways. These disturbances include phenylalanine and tryptophan metabolism pathways, mitochondrial dysfunction, oxidative stress, dopaminergic synapse, and synaptic vesicle cycle.

Parkinson’s disease occurs when there is damage to the dopaminergic nerve cells (i.e., those activated by or sensitive to dopamine) in the brain that are responsible for dopamine production, one of the primary neurotransmitters mediating motor function. Although the cause of dopaminergic cell damage remains unknown, evidence suggests that pesticide exposure, especially chronic exposure, may be the culprit. Occupational exposure poses a unique risk, as pesticide exposure is direct via handling and application. A 2017 study finds that occupational use of pesticides (i.e., fungicides, herbicides, or insecticides) increases PD risk by 110 to 211 percent. Even more concerning is that some personal protection equipment (PPE) may not adequately protect workers from chemical exposure during application. However, nonoccupational (residential) pesticide exposure, such as proximity to pesticide-treated areas, also presents a risk for PD development. A Louisiana State University study finds that residents living adjacent to pesticide-treated pasture and forest from the agriculture and timber industry have higher rates of PD incidence. Furthermore, pesticide residue in waterways and on produce present an alternate route for residential pesticide exposure to increase the risk for PD via ingestion. Pesticide contamination in waterways is historically commonplace and widespread in U.S. rivers and streams, with over 90 percent of water samples containing at least five or more pesticides. Pesticide exposure can cause severe health problems even at low residue levels, including endocrine disruptioncancersreproductive dysfunctionrespiratory problems (e.g., asthma, bronchitis), neurological impacts (e.g., developmental effects and Parkinson’s), among others. Nevertheless, direct occupational and indirect nonoccupational exposure to pesticides can increase the risk of PD

This study is the first to thoroughly investigate the molecular mechanisms involved in PD symptom development from maneb exposure, indicating a reduction of neurotransmitters and disturbance of neurotransmission systems. However, prior studies indicate that a pathological (disease-causing) agent, like pesticides, may infiltrate the nervous system via the olfactory bulb, gut, or both and circulate throughout the nervous system to increase PD risk. This study adds to the large body of scientific studies strongly implicating pesticide’s involvement in Parkinson’s disease development. Pesticides themselves, mixtures of chemicals such as Agent Orange (2,4-D and 2,4,5-T) or dioxins, and therapeutic hormones or pharmaceutical products can possess the ability to disrupt neurological function. Moreover, 90 percent of Americans have at least one pesticide compound in their body, primarily from dietary exposure, like food and drinking water. These toxic compounds have a global distribution, with evaporation and precipitation facilitating long-range atmospheric transport, deposition, and bioaccumulation of hazardous chemicals in the environment. Thus, exposure to these toxicants can cause several adverse environmental and biological health effects. With the increasing ubiquity of pesticides, current measures safeguarding against pesticide use must adequately detect and assess total chemical contaminants. Therefore, the impacts of pesticides on the nervous system, including the brain, are hazardous, especially for chronically exposed individuals (e.g., farm workers) or during critical windows of vulnerability and development (e.g., childhood, pregnancy). Considering health officials expect Parkinson’s disease diagnoses to double over the next 20 years, it is essential to mitigate preventable exposure from disease-inducing pesticides.

Although the exact cause of PD remains unknown, studies continuously identify pesticide exposure and specific gene-pesticide interactions as significant adverse risk factors. However, only a small percentage of PD is genetic, and PD is quickly becoming “the world’s fastest-growing brain disease.” Therefore, research like this is vital for examining how various pesticides and their exposure routes present potential risk factors for developing diseases like Parkinson’s. Environmental triggers like occupational exposure to pesticides can prompt PD in individuals with or without the genetic precursor.

The scientific literature demonstrates pesticides’ long history of severe adverse effects on human health (i.e., endocrine disruption, cancer, reproductive/birth problems, neurotoxicity, loss of biodiversity, etc.) and wildlife and biodiversity. In addition to this research, several studies demonstrate autism, mood disorders (e.g., depression), and degenerative neurological conditions (e.g., ALSAlzheimer’sParkinson’s) among aquatic and terrestrial animals, including humans, exposed to pesticides. However, there are several limitations in defining real-world poisoning as captured by epidemiologic studies in Beyond Pesticides’ Pesticide-Induced Diseases Database. The adverse health effects of pesticides, exposure, and the aggregate risk of pesticides showcase a need for more extensive research on occupational and nonoccupational pesticide exposure, especially in agriculture. For more information on the effects of pesticide exposure on neurological health, see PIDD pages on Parkinson’s diseasedementia-like diseases, such as Alzheimer’s, and other impacts on cognitive function

Parkinson’s disease has no cure, but preventive practices like organics can eliminate exposure to toxic PD-inducing pesticides. Organic agriculture represents a safer, healthier approach to crop production that does not necessitate pesticide use. Beyond Pesticides encourages farmers to embrace regenerative, organic practices and consumers to purchase organically grown food. A complement to buying organic is contacting various organic farming organizations to learn more about what you can do. Those affected by pesticide drift can refer to Beyond Pesticides’ webpage on What to Do in a Pesticide Emergency and contact the organization for additional information. Furthermore, see Beyond Pesticides’ Parkinson’s Disease article from the Spring 2008 issue of Pesticides and You.

All unattributed positions and opinions in this piece are those of Beyond Pesticides.

Source: Zhongnan University and Shandong University

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