Design and Development of Structure-Based Small Molecule Inhibitors of Amyloid β-Protein Assembly and Neurotoxicity.
We are developing novel compounds that inhibit the formation of that toxic protein aggregates that cause Alzheimer's disease, including those of amyloid β-protein and tau. We use a rational, structure-based approach in the design of the compounds, based on the latest knowledge of the molecular interactions and forces that control the formation of the aggregation process. Unlike traditional attempts to develop inhibitors of protein self-assembly, which have focused on disruption of a protein structure called β-pleated sheet, our compounds interfere with particular sets of molecular interactions that happen during the initial self-assembly steps of these proteins, before formation of β-pleated sheets.
|Sponsors:||Jim Easton Consortium for Alzheimer's Disease Drug Development and Biomarker Discovery at UCLA, American Health Assistance Foundation, UCLA Center for Gene-Environment Studies in Parkinson's Disease, Michael J. Fox Foundation, Team Parkinson/Parkinson Alliance and RJG Foundation.|
|Principal Investigator:||Gal Bitan, PhD|
|Collaborators:||Thomas Schrader, PhD and Frank Klärner, PhD from University of Duisburg-Essen, Germany, and Sally Frautschy, PhD, Jeff Bronstein, MD, PhD, and Marie-Françoise Chesselet, MD, PhD from University of California, Los Angeles, USA.|