(Beyond Pesticides, June 28, 2011) Recent studies have linked Parkinsonâ€™s disease to pesticide exposure. In a new article published in the journal Molecular Neurodegeneration, researchers at the University of Missouri School of Medicine take some of the first steps toward understanding this link and unraveling the molecular dysfunction that occurs when proteins are exposed to environmental toxins. The study, “Oxidation of the cysteine-rich regions of parkin perturbs its E3 ligase activity and contributes to protein aggregation,” helps further explain recent NIH findings that demonstrate the link between Parkinson’s disease and two particular pesticides â€” rotenone and paraquat.
“Fewer than 5 percent of Parkinson’s cases are attributed to genetics, but more than 95 percent of cases have unknown causes,” said Zezong Gu, MD, PhD, assistant professor of pathology and anatomical sciences. “This study provides the evidence that oxidative stress, possibly due to sustained exposure to environmental toxins, may serve as a primary cause of Parkinson’s. This helps us begin to unveil why many people, such as farmers exposed to pesticides, have an increased incidence of the disease.”
Scientists previously understood that Parkinson’s is associated with oxidative stress, which is when electronically unstable atoms or molecules damage cells. The MU study yields more specific information about how oxidative stress causes parkin, a protein responsible for regulating other proteins, to malfunction.
Dr. Gu and his Sanford-Burnham Medical Research Institute colleagues invented a new antibody that allowed them to detect how oxidative stress affected proteins when exposed to a variety of environmental toxins, such as the pesticide rotenone. They then specifically demonstrated how oxidative stress caused parkin proteins to cluster together and malfunction, rather than performing normally by cleaning up damaged proteins.
“This whole process progresses into Parkinson’s disease,” Dr. Gu said. “We illustrated the molecular events that lead to the more common form of the disorder in the vast majority of cases with unknown causes. Knowing this, we can find ways to correct, prevent and reduce the incidence of this disease.”
Researchers used mass spectrometry to analyze findings. They measured parkin fragments, pinpointed whether the proteins were modified and where that modification occurred. This enabled them to map the location of parkin oxidation and further compare these events with genetic mutations in patients with Parkinson’s disease reported in the literature. Their findings demonstrated that parkin protein oxidation in certain locations corresponds with the location of mutations. They then sought to determine the outcome of the modification â€” finding their results to be consistent in multiple disease models, including cell cultures and tissue samples from rodents, monkeys and human postmortem Parkinson’s patients.
The second most common neurodegenerative disease, Parkinsonâ€™s disease occurs when nerve cells in the substantia nigra region of the brain are damaged or destroyed and can no longer produce dopamine, a nerve-signaling molecule that helps control muscle movement. People with Parkinsonâ€™s have a variety of symptoms including loss of muscle control, trembling and lack of coordination. They may also experience anxiety, constipation, dementia, depression, urinary difficulties, and sleep disturbances. Over time, symptoms intensify. At least one million Americans have Parkinsonâ€™s and about 50,000 new cases are diagnosed each year. With less than one percent of cases caused by genetics, researchers have been looking for the potential risk factors for developing Parkinsonâ€™s disease.
For more information on the link between pesticides and common diseases and disorders, see Beyond Pesticidesâ€™ Pesticide-Induced Diseases Database.