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Penn study shows how misfolded proteins are selected for disposal
Date:5/29/2014

PHILADELPHIA It's almost axiomatic that misfolded proteins compromise how cells normally function and cause debilitating human disease, but how these proteins are detected and degraded within the body is not well understood. Neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis (Lou Gehrig's disease), Huntington's disease, and spinocerebellar ataxias exact a devastating toll on aging populations throughout the world.

"Yet, there is virtually no cure for any of these diseases, and clinical trials have yielded mostly disappointing results, indicating that investigators are missing something fundamental about these diseases," says Xiaolu Yang, PhD, professor of Cancer Biology, Perelman School of Medicine at the University of Pennsylvania. All of these diseases are caused by the accumulation of toxic misfolded proteins in different types of neurons. "However, our knowledge about how cells normally remove these proteins, an issue fundamental to understanding what goes wrong in neurodegenerative diseases, is very limited."

Yang and first author Lili Guo, PhD, who was a doctoral student in the Yang lab, identified a protein recycling pathway in mammalian cells that removes misfolded proteins. Their findings appear online today in Molecular Cell ahead of the print edition. They also demonstrated this pathway's role in protecting against neurodegenerative diseases in an animal model. Guo is now a postdoctoral fellow in another Perelman School lab.

Proteins are the work horses of the cells. They are the most abundant macromolecules, extremely versatile in their functions and critically important for virtually all biological processes. However, proteins are also highly prone to misfolding due to genetic mutations, synthetic inaccuracies, and irreparable damages. What's more, the half-life of many proteins is relatively short, from a few minutes to a few hours, necessitating their continued
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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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