Link Between Pesticides and Parkinson’s Disease Identified
Pesticides have long been thought to be involved in the pathology of PARKINSON’S DISEASE, but finding a definite link has been a near impossibility. Many researchers spending many years of research sought to find this elusive relationship, and their primary theory has finally proven correct. But it took some very advanced, newly developed technological research skills and two major teams of researchers to unlock the clues.
Past studies had shown there were increased risks to certain populations, such as farmers and others who were exposed to pesticides; however there were always people who never showed any response to their exposure. Why were some folks more likely to develop PARKINSON’S DISEASE while others did not? As the relatively new studies of genetics have advanced, the connection between genes and pesticides became clear.
Researchers at the Burnham Institute in La Jolla, California together with another team from the Whitehead Institute of the Massachusetts Institute of Technology in Cambridge, MA. used skin cells collected from people with PARKINSON’S DISEASE that carried the genetic mutation for alpha synuclein, the signature protein found in Lewy bodies. From these skin cells, they induced human pluripotent stem cells to grow. Pluripotent stem cells are able to develop into various specific types of cells when properly stimulated. In the cells that they grew, they removed the genetic mutation for alpha synuclein in half of them and left it in the others. They then programmed the cells to grow into the dopamine containing neurons found in PARKINSON’S DISEASE and began exposing both sets to various pesticides in varying amounts.
When they began to study the results of these exposures, the cells that carried the genetic mutation for alpha synuclein became damaged and cell death soon followed. Those without the mutation survived. So they started looking closer and found that in the cells with the genetic mutation, a vital mitochondrial pathway that protects cells with dopamine was interrupted, causing the cells to die. In the non mutation carrying cells, this pathway would protect the cells and keep them alive and functional.
This study has shown beyond a doubt the relationship between the environment and a person’s genetics. But while it has found one channel affecting dopamine neurons, this does not rule out that there may be many other mutations or pathways that could also be affected. Stuart Lipton, one of the lead researchers on this project says: “In the future, we anticipate using the knowledge of mutations that predispose an individual to these disease in order to predict who should avoid a particular environmental exposure. Moreover, we will be able to screen for patients who may benefit from a specific therapy that can prevent, treat or possibly cure these diseases.”
Not being content merely to identify the problem, another principal investigator on this study decided to search for a solution to the problem. Rajesh Ambasudhan explains: “Once we understood the pathway and the molecules that were altered by the pesticides, we used high-throughput screening to identify molecules that could inhibit the effect… One molecule we identified was isoxazole, which protected mutant neurons from cell death induced by the tested pesticides.” This molecule is currently used in other drugs already approved by the Food and Drug Administration, so it may be possible to quickly find a way to repurpose these medications to provide an early treatment for Parkinson’s disease.
Cell, November 27, 2013; NIH, P01 HD29587, P01 ES016738, and P30 NS076411, R37 CA084198
“Isogenic human iPSC Parkinson’s model shows nitrosative stress-induced dysfunction in MEF2-PGC1a transcription”
Cell, December 5, 2013.
Scott D. Ryan (1,*) Nima Dolatabadi (1,*), Shing Fai Chan (1), Xiaofei Zhang (1), Mohd Waseem Akhtar (1), James Parker (1), Frank Soldner (2), Carmen R. Sunico (1), Saumya Nagar (1), Maria Talantova (1), Brian Lee (1), Kevin Lopez (1), Anthony Nutter (1), Bing Shan (3), Elena Molokanova (1), Yaoyang Zhang (3), Xuemei Han (3), Tomohiro Nakamura (1), Eliezer Masliah (5), John R. Yates III (3), Nobuki Nakanishi (1), Aleksander Y. Andreyev (4), Shu-ichi Okamoto (1), Rudolf Jaenisch (2), Rajesh Ambasudhan (1), and Stuart A. Lipton (1,5).
Review by Marcia McCall