For your Dad
Parkinson Gene Link May Aid Battle Against Disease
Oct. 20, 2014
AUSTIN, Texas — A research lab at The University of Texas at Austin has identified the function of a gene believed to play a critical role in parkinsonian disorders.
Dr. Somshuvra Mukhopadhyay, assistant professor of pharmacology and toxicology, led the research team that focused on the gene SLC30A10 and its role as a “door opener” in helping to remove elevated levels of manganese from cells. The study was published in the Oct. 15 issue of The Journal of Neuroscience.
“Manganese is essential for life, but elevated levels are toxic,” Mukhopadhyay said, adding that excessive amounts of the metal eventually make their way into the blood stream and then to the brain where they kill neurons and cause parkinsonism.
The link is considered a major step in the process of finding an effective treatment for parkinsonian disorders, including Parkinson’s disease, which affects more than a half million people in the United States alone. There is no known cure for any form of parkinsonism.
Parkinsonian disorders usually occur because of a combination of genetic and environmental factors. Exposure to the metal manganese is an environmental factor known to cause parkinsonism in humans. Manganese-induced parkinsonism is most often seen in individuals with documented exposures to manganese. Exposures may originate from occupational sources such as in welding and mining professions; through environmental sources such as consuming tainted drinking water and food sources; and as a result of disease such as cirrhosis of the liver and alcoholism, which block manganese excretion.
Prior studies of a cohort of European families that exhibited hereditary parkinsonism led earlier researchers to look at a genetic link. The families’ genomes were sequenced, leading to the discovery that all family members with the disease had mutations in SLC30A10. The gene was believed to be a key element, but its role and function were not determined.
Mukhopadhyay and his team discovered that the protein coded by the gene resides on the surface of the cell and works as a transporter to escort or remove excessive levels of manganese from the cell. Mutations of the gene, as seen in the research family, impede this function as they cause the gene to become trapped within the cell and thus fail in its work to transport excessive metals from the cell. Patients then retain excessive amounts of manganese within their cells and develop parkinsonism because of manganese toxicity.
“The gene basically acts as a door opener to release the excess metal from the cell,” the researcher said.
![](https://webarchive.library.unt.edu/dentonfracking/20141022185213im_/http://www.utexas.edu/news/files/parkinsons-fig-box.jpg)
These images depict two nerve cells. The image on the left shows the action of healthy SLC30A10 at full function, including acting as gate keeper to aid in removing excessive levels of manganese from the cell. The image on the right shows the disease-causing mutation of the same gene as it is shriveled and dying.
Defining the function of the gene is critical, he said, adding that these findings provide a unique insight into how interactions between a genetic mutation (mutations in SLC30A10) and an environmental factor (manganese) come together to cause parkinsonism in humans. Researchers can now focus on developing effective treatments by developing drugs that enhance the efflux activity of the gene to treat patients who carry mutations in this gene. Such treatments also are expected to be beneficial for patients who suffer from manganese-induced parkinsonism stemming from exposure to elevated manganese but who do not have mutations in SLC30A10.
The UT Austin team worked in partnership with a team from the Albert Einstein College of Medicine led by Dr. Michael Aschner. Others from UT Austin involved in the study: Dinorah Leyva-Illades, a former postdoctoral student; Charles E. Zogzas and Caleb D. Swaim, graduate students; Jonathan M. Mercado, an undergraduate student; and Steve Hutchens, lab manager for Mukhopadhyay. Dr. Richard Morrisett, a professor of pharmacology and toxicology, provided technical expertise. This work was supported by a grant from the National Institutes of Health to Mukhopadhyay.
For more information, contact: University Communications, Office of the President, 512 471 3151; Vicki Matustik, College of Pharmacy, 512-232-1769.
1. elizabethhughesphd@sbcglobal.net said on Oct. 20, 2014