UNMC Scientists Make Advances in Parkinson's Disease

by Ethan Hamilton, Samatha Mosley and Catherine Lehn
January 14, 2008
http://www.newsnetnebraska.org/vnews.../478bdd54b616b

New journal articles published by scientists at the University of Nebraska Medical College detailed their findings of causes and the progression of Parkinson's disease according to a UNMC press release. This will allow scientists to work towards more efficient treatments, therapies and vaccines for the disease that affects nearly one million Americans.

"Our research presents conclusive evidence through four stories in mice and using human autopsy tissue that nitrated alpha-synuclein induces toxic inflammatory effects, which are detrimental to healthy neurons. It also incites elements of the immune system in and outside the brain," said R. Lee Mosley, Ph.D., co-investigator for these studies and an assistant professor of pharmacology and experimental neuroscience at UNMC.

In the brains' of Parkinson's patients, nerve cells die which results in a reduced amount of dopamine. The loss of dopamine causes loss of motor skills and tremors.

Although the cause of Parkinson's disease is unknown, scientists have discovered mutations in alpha-synucein, a brain protein. This brain protein helps cells communicate. When the protein is altered in Parkinson's disease patients, the functionality of alpha-synucein changes due to local inflammatory responses.

Researchers at UNMC discovered when the alpha-synuclein is modified, its support function deteriorates. In addition, the disease weakens the immune system which allows Parkinson's disease to accelerate.

"Many scientists had previously thought that alpha-synuclein engagement of the immune system would inhibit Parkinson's disease progression because of antibodies produced against the protein would serve to break down the insoluble proteins formed when alpha-synuclein becomes modified," said Dr. Howard Gendelman, chairman of the pharmacology and experimental neuroscience and director of the Center for Neurovirology and Neurodegenerative Disorders at UNMC. "But this same protein also increases immune reactions that prove toxic to the brain in so doing speed the disease."

Laboratories of Kalipada Pahan, Ph.D., of Rush Medical School in Chicago, and Serge Przedborksi, Ph.D., of Columbia University Medical Center in New York contributed to these findings.