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   PID: hpt/lnx 1.9.0-cur 2019-01-08   
   TID: hpt/lnx 1.9.0-cur 2019-01-08   
    10 pesticides toxic to neurons involved in Parkinson's    
    With thousands of pesticides in use, the researchers' new screening   
   approach could make it easier to determine which ones are linked to the disease   
      
      
     Date:   
         May 18, 2023   
     Source:   
         University of California - Los Angeles Health Sciences   
     Summary:   
         Through a novel pairing of epidemiology and toxicity screening,   
         researchers were able to identify 10 pesticides that were directly   
         toxic to key neurons.   
      
      
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   FULL STORY   
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   Researchers at UCLA Health and Harvard have identified 10 pesticides   
   that significantly damaged neurons implicated in the development of   
   Parkinson's disease, providing new clues about environmental toxins'   
   role in the disease.   
      
   While environmental factors such as pesticide exposure have long been   
   linked to Parkinson's, it has been harder to pinpoint which pesticides   
   may raise risk for the neurodegenerative disorder. Just in California,   
   the nation's largest agricultural producer and exporter, there are nearly   
   14,000 pesticide products with over 1,000 active ingredients registered   
   for use.   
      
   Through a novel pairing of epidemiology and toxicity screening that   
   leveraged California's extensive pesticide use database, UCLA and Harvard   
   researchers were able to identify 10 pesticides that were directly   
   toxic to dopaminergic neurons. The neurons play a key role in voluntary   
   movement, and the death of these neurons is a hallmark of Parkinson's.   
      
   Further, the researchers found that co-exposure of pesticides that are   
   typically used in combinations in cotton farming were more toxic than   
   any single pesticide in that group.   
      
   For this study, published May 16 in Nature Communications, UCLA   
   researchers examined exposure history going back decades for 288   
   pesticides among Central Valley patients with Parkinson's disease who had   
   participated in previous studies. The researchers were able to determine   
   long-term exposure for each person and then, using what they labeled a   
   pesticide-wide association analysis, tested each pesticide individually   
   for association with Parkinson's. From this untargeted screen, researchers   
   identified 53 pesticides that appeared to be implicated in Parkinson's --   
   most of which had not been previously studied for a potential link and   
   are still in use.   
      
   Those results were shared for lab analysis led by Richard Krolewski, MD,   
   PhD, an instructor of neurology at Harvard and neurologist at Brigham   
   and Women's Hospital. He tested the toxicity for most of those pesticides   
   in dopaminergic neurons that had been derived from Parkinson's patients   
   through what's known as induced pluripotent stem cells, which are a type   
   of "blank slate" cell that can be reprogrammed into neurons that closely   
   resemble those lost in Parkinson's disease.   
      
   The 10 pesticides identified as directly toxic to these neurons   
   included: four insecticides (dicofol, endosulfan, naled, propargite),   
   three herbicides (diquat, endothall, trifluralin), and three fungicides   
   (copper sulfate [basic and pentahydrate] and folpet). Most of the   
   pesticides are still in use today in the United States.   
      
   Aside from their toxicity in dopaminergic neurons, there is little that   
   unifies these pesticides. They have a range of use types, are structurally   
   distinct, and do not share a prior toxicity classification.   
      
   Researchers also tested the toxicity of multiple pesticides that are   
   commonly applied in cotton fields around the same time, according to   
   California's pesticide database. Combinations involving trifluralin, one   
   of the most commonly used herbicides in California, produced the most   
   toxicity. Previous research in the Agricultural Health Study, a large   
   research project involving pesticide applicators,had also implicated   
   trifluralin in Parkinson's.   
      
   Kimberly Paul, PhD, a lead author and assistant professor of neurology at   
   UCLA, said the study demonstrated their approach could broadly screen for   
   pesticides implicated in Parkinson's and better understand the strength   
   of these associations.   
      
   "We were able to implicate individual agents more than any other   
   study has before, and it was done in a completely agnostic manner,"   
   Paul said. "When you bring together this type of agnostic screening   
   with a field-to-bench paradigm, you can pinpoint pesticides that look   
   like they're quite important in the disease."  The researchers are   
   next planning to study epigenetic and metabolomic features related   
   to exposure using integrative omics to help describe which biologic   
   pathways are disrupted among Parkinson's patients who experienced   
   pesticide exposure. More detailed mechanistic studies of the specific   
   neuronal processes impacted by pesticides such as trifluralin and copper   
   are also underway at the Harvard/Brigham and Women's labs. The lab work   
   is focused on distinct effects on dopamine neurons and cortical neurons,   
   which are important for the movement and cognitive symptoms in Parkinson's   
   patients, respectively. The basic science is also expanding to studies of   
   pesticides on non-neuronal cells in the brain - - the glia -- to better   
   understand how pesticides influence the function of these critical cells.   
      
   Other authors include Edinson Lucumi Moreno, Jack Blank, Kristina   
   M. Holton, Tim Ahfeldt, Melissa Furlong, Yu Yu, Myles Cockburn, Laura   
   K. Thompson, Alexander Kreymerman, Elisabeth M. Ricci-Blair, Yu Jun   
   Li, Heer B. Patel, Richard T Lee, Jeff Bronstein, Lee L. Rubin, Vikram   
   Khurana, and Beate Ritz.   
      
       * RELATED_TOPICS   
             o Health_&_Medicine   
                   # Parkinson's_Research # Chronic_Illness #   
                   Diseases_and_Conditions # Nervous_System   
             o Mind_&_Brain   
                   # Parkinson's # Disorders_and_Syndromes # Caregiving #   
                   Psychology   
       * RELATED_TERMS   
             o Protein_microarray o Personalized_medicine o Sensory_neuron   
             o Neuron o Neural_network o Mushroom_poisoning o Neurobiology   
             o Tropospheric_ozone   
      
   ==========================================================================   
   Story Source: Materials provided by   
   University_of_California_-_Los_Angeles_Health_Sciences.   
      
   Note: Content may be edited for style and length.   
      
      
   ==========================================================================   
   Journal Reference:   
      1. Kimberly C. Paul, Richard C. Krolewski, Edinson Lucumi Moreno, Jack   
         Blank, Kristina M. Holton, Tim Ahfeldt, Melissa Furlong, Yu Yu,   
         Myles Cockburn, Laura K. Thompson, Alexander Kreymerman, Elisabeth   
         M. Ricci- Blair, Yu Jun Li, Heer B. Patel, Richard T. Lee, Jeff   
         Bronstein, Lee L.   
      
         Rubin, Vikram Khurana, Beate Ritz. A pesticide and iPSC dopaminergic   
         neuron screen identifies and classifies Parkinson-relevant   
         pesticides.   
      
         Nature Communications, 2023; 14 (1) DOI: 10.1038/s41467-023-38215-z   
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   Link to news story:   
   https://www.sciencedaily.com/releases/2023/05/230518120851.htm   
      
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