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First mouse model for multiple system atrophy points to new treatment targets for brain diseases

(Philadelphia, PA) A newly developed animal model for Multiple System Atrophy (MSA) a collection of neurodegenerative disorders once thought to be three separate diseases sheds new light on this little-studied brain disease, according to research from investigators at the University of Pennsylvania School of Medicine.

Virginia M.-Y. Lee, PhD, Director of Penn's Center for Neurodegenerative Disease Research, and colleagues demonstrated that the mice showed symptoms similar to human MSA. These include an accumulation of a protein called -synuclein in oligodendrocytes cells that produce the protective myelin sheath that covers axons. This protein accumulation disables oligodendrocytes, leading to a loss of the sheath on neurons and eventually nerve-cell malfunction and death. The mice also showed slowly progressive problems with their motor skills associated with the nerve-cell damage. Neurons are important in transmitting signals and in maintaining learning and memory.

"The uniqueness of this disease is that, unlike most of the neurodegenerative diseases, which affect neurons primarily and oligodendrocytes secondarily, this is the other way around," says Lee. In fact, there is growing evidence that non-neuronal cells also play a role in amyloid deposits in Alzheimer's disease and amyotrophic lateral sclerosis (ALS) mouse models. Lee and colleagues report their findings in the March 24, 2005 issue of Neuron.

MSA is so named because it affects multiple parts of the nervous system. Initially MSA was given three names, based on the symptoms physicians had observed. However, when they closely examined patients' pathology, the disorders seemed related, based on the -synuclein proteins in cells. In the clinic, many patients with MSA present with symptoms similar to Parkinson's disease (PD), and MSA has been misdiagnosed as such.

Collectively, MSA now includes three related disorders characterized by their most prominent symptoms: olivopo
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Contact: Karen Kreeger
karen.kreeger@uphs.upenn.edu
215-662-2560
University of Pennsylvania School of Medicine
23-Mar-2005


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