Thursday, February 5, 2009, Condensed Matter Biological Physics Seminar, Gal Bitan, David Geffen School of Medicine, UCLA, "Inhibitors of Amyloid Assembly - Challenges and Solutions", 4:30 PM, Doherty Hall A310, CMU
 

Abstract:

In amyloid-related diseases, including Alzheimer's, Parkinson's, and type 2 diabetes, toxic oligomers of "amyloidogenic'' proteins disrupt normal cellular and tissue function leading to progressive disease and often death. To date, none of these diseases can be prevented or cured. As many of these diseases are age-related, finding disease-modifying therapies is a particularly urgent goal in view of the increasing human life span in recent decades. Inhibition of protein self-assembly is highly challenging because the binding energy that leads to formation of toxic assemblies comprises multiple weak interactions and is spread across a wide area. In addition, amyloid protein oligomers constantly change and do not have a stable structure. Traditional high-throughput screening approaches that have been useful for identifying enzyme inhibitors or receptor antagonists have had little success producing effective anti-amyloid drug leads. Based on current knwledge of the interactions that control amyloid assembly, we have been able to produce effective inhibitors of amyloid proteins using rational design approaches. In my seminar, I will discuss recent results of these approaches leading to the discovery of novel peptide and small molecule inhibitors, and our current understanding of their mechanism of action.