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

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.”
 

This story appears in Penn Medicine's Basic Science News Bites (December 2009). Also in this edition:

  • Orthopaedics Research
  • picThrowing Their Backs into Regenerative Medicine
  • In order for tissue grown in the lab to replace damaged or diseased tissue in the body, it needs to withstand complex mechanical loads – large forces regularly experienced over a lifetime of daily activities.
  • Cell Biology
  • picCheating a Cell's Demise
  • The lifespan of normal human cells is determined in part by telomeres – the DNA-protein structures that cap the beginnings and ends of chromosomes.
  • Neuroscience Research
  • picPrion-Busting Cocktails
  • Prions are proteins that act like germs, infecting healthy tissue and causing havoc in the body. Their extreme stability and shape-shifting abilities make prions exceptionally difficult drug targets.
  • Diabetes Research
  • picNew Insights on Insulin Resistance
  • The overwhelming majority of type 2 diabetics are insulin resistant, which means their bodies are unable to respond to and use the insulin they produce.
  • Genetics Research
  • picZebrafish Model of Common Genetic Disorder
  • Because zebrafish develop rapidly, are transparent when young, and can be easily bred in large numbers, this new animal model will dramatically increase the screening capacity for a common human inherited disorder.

 

 
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