Now, new research has identified a common genetic risk factor for heart failure in Caucasians that is also linked to kidney function. The study, a collaboration between the Perelman School of Medicine, Washington University School of Medicine, and other institutions, was published online this week in The Proceedings of the National Academy of Sciences.
Alpha-synuclein (a-syn) is a brain protein that forms clumps called Lewy bodies, the hallmark of PD and other neurodegenerative disorders.
In earlier studies at other institutions, when fetal nerve cells were transplanted into the brains of PD patients, some of the transplanted cells developed Lewy bodies. This suggests that healthy cells take up abnormal extracellular a-syn, which “recruits” normal a-syn into clumps. However, it is not clear whether the Lewy bodies were formed by the spread of abnormal a-syn fibrils or if the neighboring diseased neurons exerted some other toxic influence that caused young grafted neurons to form Lewy bodies.
“We examined whether exposure of neurons to a-syn fibrils recruited normal a-syn in these neurons to form Lewy bodies,” explains senior author Virginia M.-Y Lee, PhD, director of the Center for Neurodegenerative Disease Research and professor of Pathology and Laboratory Medicine. “We performed our experiments using synthetic a-syn fibrils and normal neurons, similar to the physiological conditions seen in the majority of sporadic PD patients.”
They found that the a-syn fibrils acted as “seeds” that induced normal a-syn to aggregate into clumps. The fibrils were taken up by nerve cell extensions, spread to the cell body where PD-like Lewy bodies formed that impaired neuronal function and led to the death of this neuron. This suggests that abnormal a-syn can amplify and propagate PD-like Lewy bodies throughout the nervous system.
This research was funded by the National Institutes of Health for the Penn Udall Center, the Picower Foundation, the Jeff Keefer Foundation, the Parkinson Council, and the Stein-Bellet Family Foundation.
Penn Medicine is one of the world’s leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation’s first medical school) and the University of Pennsylvania Health System, which together form a $4 billion enterprise.
Penn’s Perelman School of Medicine is currently ranked #2 in U.S. News & World Report’s survey of research-oriented medical schools and among the top 10 schools for primary care. The School is consistently among the nation’s top recipients of funding from the National Institutes of Health, with $507.6 million awarded in the 2010 fiscal year.
The University of Pennsylvania Health System’s patient care facilities include: The Hospital of the University of Pennsylvania — recognized as one of the nation’s top 10 hospitals by U.S. News & World Report; Penn Presbyterian Medical Center; and Pennsylvania Hospital – the nation’s first hospital, founded in 1751. Penn Medicine also includes additional patient care facilities and services throughout the Philadelphia region.
Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2010, Penn Medicine provided $788 million to benefit our community.