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New class of compounds discovered for potential Alzheimer's disease drug
Date:8/10/2009

PHILADELPHIA A new class of molecules capable of blocking the formation of specific protein clumps that are believed to contribute to Alzheimer's disease pathology has been discovered by researchers at the University of Pennsylvania School of Medicine. By assaying close to 300,000 compounds, they have identified drug-like inhibitors of AD tau protein clumping, as reported in the journal Biochemistry.

Co-authors Alex Crowe, Research Specialist; Kurt R. Brunden, PhD, Director of Drug Discovery at Penn's Center for Neurodegenerative Disease Research (CNDR); Virginia M.-Y. Lee, PhD, and John Q. Trojanowski, MD, PhD, CNDR Co-Directors, and colleagues conducted the screen to find small molecules that prevent the formation of the tau protein fibrils. These fibrils, a hallmark pathological feature of AD, have been a holy grail for investigators hoping to better treat AD and related neurodegenerative diseases.

Tau fibrils accumulate as insoluble deposits in brain nerve cells of patients with a host of debilitating neurodegenerative diseases, the most prevalent of which is AD. Since these tau aggregates are found in several neurodegenerative disorders and are thought to contribute to disease pathology, it is hoped that drugs that prevent these deposits might prove to be effective therapeutic agents for AD and related disorders. This is the largest drug screen completed to date using the compound repository housed at the National Institutes of Health (NIH) Chemical Genomics Center.

Small molecules that prevent or reverse tau clumping might have therapeutic value, explains Brunden. Examples of such compounds have been described previously but nearly all have properties, such as chemical reactivity, poor absorption by the gut, or poor brain penetration, that render them unsuitable as drug candidates.

The test-tube-based assay used to screen the large NIH library was designed by Dr. Lee to see if each compound could block fibr
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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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