There are a million ways to muck up a nerve cell. In the case of Parkinson’s disease, Lewy bodies are abnormal clumps that develop inside brain cells, whose primary component is the protein alpha-synuclein. These clumps can eventually lead to the devastating muscle and neurodegenerative symptoms of Parkinson’s.
Lewy bodies. Credit: Kevin Luk, PhD.
To find new drugs, researchers have created a living-cell model of alpha-synuclein clumps, which mimic Lewy bodies seen in the tissue of Parkinson's disease patients. This model gives investigators a new way to investigate the biology and pathology of Parkinson’s in cultured cells, which has not been possible to date, according to research recently published in the Proceedings of the National Academy of Sciences.
This new system will now allow investigators to test compounds that might block or reverse the formation of fibrils made of alpha-synuclein, say co-authors, Virginia M.-Y. Lee, PhD, director of Penn's Center for Neurodegenerative Disease Research, John Q. Trojanowski, MD, PhD, director of Penn's Institute on Aging, and postdoctoral fellow Kelvin Luk, PhD. They hope to use the model system to better understand mechanisms of Parkinson’s as well as accelerate the pace of drug discovery.
“We hope that this cell culture model system will be like that of models developed for a-beta protein clumping in Alzheimer’s disease,” says Lee. “That living-cell model has been helpful for screening and discovering a-beta-lowering drugs for Alzheimer's.”