Jeff Bronstein, M.D., Ph.D.
University of California, Los Angeles
P01ES016732, R21ES16446, T32ES01545
A new study by NIEHS-funded researchers uncovered information linking a common group of pesticides with Parkinson’s disease and revealed how a drug may protect against the chemical-induced pathway to the disease. Using zebrafish, they found that getting rid of the protein alpha-synuclein, a potential target for therapeutics, protected against toxicity of the pesticide ziram. Ziram is used extensively in agriculture, and has been previously linked to an increased risk of developing Parkinson’s disease, but the mechanism was not clearly understood.
In the study, researchers began by exposing zebrafish to ziram and found that it led to loss of dopaminergic neurons, the main source of dopamine to the central nervous system, and abnormal swimming behavior — both signs of a Parkinson’s-like condition. To determine if alpha-synuclein proteins contributed to the changes, the researchers genetically eliminated the alpha-synuclein proteins and observed that these zebrafish were protected from the signs of a Parkinson’s-like condition. They also discovered that the investigational drug CLR01, which is being developed to break up protein aggregates in Parkinson’s patients, provided protection from the Parkinson’s-like condition in normal zebrafish.
The scientists found that either getting rid of the alpha-synuclein protein or breaking up its aggregates protect the zebrafish against ziram toxicity. These findings could potentially extend to other chemicals that may induce Parkinson’s disease, a disease in which more than 70 percent of cases cannot be explained by genetics.
Citation: : Lulla A, Barnhill L, Bitan G, Ivanova MI, Nguyen B, O'Donnell K, Stahl MC, Yamashiro C, Klärner FG, Schrader T, Sagasti A, Bronstein JM. 2016. Neurotoxicity of the Parkinson's disease-associated pesticide ziram Is synuclein-dependent in zebrafish embryos. Environ Health Perspect; doi:10.1289/ehp141 [Online 15 June 2016].