The causes of Parkinson’s are not known in most cases, although it is known that there are genetic and environmental factors involved in its appearance and exposure to pesticides has long been associated with the development of this disease. Now, UCLA Health and Harvard scientists have identified 10 pesticides that significantly impair the dopaminergic neurons whose dysfunction causes Parkinson’s, a finding that may shed light on the impact of environmental toxins on this condition.
Parkinson’s is a neurodegenerative disease in which these neurons are damaged and do not perform their task correctly, which is to produce and secrete dopamine, a neurotransmitter that is involved in movement control and the lack of which results in movement disorders experienced by patients. patients, who also often manifest other symptoms such as stiffness in the extremities, depression, and even dementia.
Thousands of pesticides are currently used, making it difficult to determine which of these substances may increase the risk of neurodegeneration. The study authors used a novel combination of epidemiology and toxicity detection leveraging the extensive database of pesticide use in California, which is considered the largest agricultural producer and exporter in the United States and where there are about 14,000 pesticide products. They contain more than 1,000 active ingredients registered for use.
The researchers were able to identify 10 pesticides that were directly toxic to dopaminergic neurons, which play a key role in voluntary movements, and whose death is a key feature of Parkinson’s disease. These scientists also found that co-exposure of pesticides normally used in combination on cotton cultivation was more toxic than any single pesticide in that group. The results have been published in Nature Communications.
Insecticides, herbicides and fungicides increase the risk of Parkinson’s
The UCLA researchers examined the exposure history—going back decades—for 288 pesticides among Central Valley patients with Parkinson’s disease who had participated in previous studies and were able to determine each individual’s long-term exposure. Then, using what they called a pesticide association analysis, they tested each pesticide individually for association with Parkinson’s. From there, they identified 53 pesticides that appeared to be involved in the disease, most of which had not been previously studied for a potential link to the disease and are still in use.
The 10 pesticides that were identified as being directly toxic to dopaminergic neurons implicated in the development of Parkinson’s included: four insecticides, three herbicides, and three fungicides.
The results were shared for the laboratory analysis led by Dr. Richard Krolewski, an instructor in neurology at Harvard and a neurologist at Brigham and Women’s Hospital, which tested the toxicity of most of these pesticides on dopaminergic neurons from Parkinson’s patients using the which are known as induced pluripotent stem cells, which are a type of “blank slate” cells that can be reprogrammed into neurons very similar to those lost to this disease.
The 10 pesticides that were identified as directly toxic to these neurons included:
- Four insecticides (dicofol, endosulfan, naled, propargite)
- Three herbicides (diquat, endothal, trifluralin)
- Three fungicides (copper sulfate [básico y pentahidratado] and folpet)
These pesticides—most of which are still used in the United States and other countries—do not share any characteristics except their toxicity to dopaminergic neurons, since they are structurally different, have diverse uses, and have not previously been included in a common toxic classification. .
Kimberly Paul, lead author and assistant professor of neurology at UCLA, said the study has shown that their approach could broadly detect pesticides implicated in Parkinson’s and better understand the strength of these associations.
The goal of these researchers is to study the epigenetic and metabolomic features associated with the use of integrated omics to help determine which biologic pathways are disrupted in Parkinson’s patients exposed to pesticides.
More detailed mechanistic studies of specific neural processes affected by pesticides such as trifluralin and copper are also underway at the Harvard and Brigham and Women’s labs, focusing on the distinct effects on dopamine neurons and cortical neurons. , which are important for movement and cognitive symptoms in Parkinson’s patients, respectively.
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