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Molecular biology of sleep apnea could lead to new treatments
Date:3/19/2008

PHILADELPHIA Researchers at the University of Pennsylvania School of Medicine have provided, for the first time, a detailed look at the molecular pathways underlying sleep apnea, which affects more than twelve million Americans, according to the National Institutes of Health. Sleep apnea is a condition characterized by temporary breathing interruptions during sleep, in which disruptions can occur dozens or even hundreds of times a night.

The team found that in an animal model of sleep apnea poorly folded proteins accumulate in one compartment of a muscle nerve cell, which, under certain conditions, tells a cell to heal itself or destroy itself. The findings appear in a recent issue of the Journal of Neuroscience.

Muscles relax as a normal part of sleep, causing the airway to close, explains senior author Sigrid C. Veasey, MD, Associate Professor of Medicine, at the Penn Center for Sleep. But in patients with sleep apnea, oxygen levels in cells drop too low, sending an arousal signal to wake by gasping for air. This happens all night long, so patients experience bad quality sleep. In addition to problems with sleepiness, subtle peripheral neural injury occurs.

In a mouse model of sleep apnea, the researchers found that motor neurons of the jaw and face had swollen endoplasmic reticula, the part of the cell where proteins get folded properly. They surmised that misfolded proteins accumulated as the endoplasmic reticula of mice were exposed to decreased oxygen and oxygen fluctuations during sleep over eight weeks. The involvement of the endoplasmic reticula has never been shown before in explaining the physiology of sleep apnea on a cellular level, says Veasey.

But how does this work? Sensor proteins sitting on the surface of the endoplasmic reticula get activated by poorly folded proteins within. The Penn group worked with one of those proteins, called PERK. When PERK gets activated, two things can happen: The cell can take a
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Contact: Karen Kreeger
karen.kreeger@uphs.upenn.edu
215-349-5658
University of Pennsylvania School of Medicine
Source:Eurekalert

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