Drug Discovery

Cognitive Enhancement

Synthetic LXRBeta Ligands in the Treatment of Alzheimer's Disease

Investigator(s): Barry Forman, Ph.D.

Institution(s): City of Hope

Duration:

Summary:

Novel anti-AD drugs are desperately needed. In this program, a novel approach to the development of drugs to reduce Aβ will be taken. The hypothesis is that Aβ in the cell is neurotoxic. Therefore, removing Aβ from the cell would be therapeutic. A receptor in the nucleus of the cell, called the LXR receptor, regulates the production of Aβ. Reduction in Aβ requires an LXR-mediated activation of the cholesterol efflux pump ABCA1. Two subtypes of LXR have been identified: LXR-α and LXR-β. The investigators have developed small molecules that selectively activate LXRβ. In this program, they will investigate these compounds in in vitro cell culture models of amyloid production. If successful, the investigators will subsequently pursue preclinical proof of concept in an animal model.