Jeff Keller, Ph.D.
University of Kentucky Research Foundation
Lexington, Kentucky

2006 Investigator-Initiated Research Grant

During the earliest stages of Alzheimer's disease, production of certain essential proteins in the brain declines. These declines likely play a role in the development of the disease. In studies of related disorders-Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis (ALS)- scientists have shown that enzymes called histone deacetylase (HDAC) inhibitors stimulate the production of essential proteins and may protect cells against pathological factors in these disorders.

Jeff Keller, Ph.D., and colleagues have been studying the effects of HDAC inhibitors on Alzheimer's disease pathology. Much of their work has involved the brains of animals genetically engineered to develop an Alzheimer-like pathology. Results so far have indicated that HDAC inhibitors help preserve normal levels of protein production in the brain and ameliorate the toxicity of beta-amyloid. Beta-amyloid is a tiny protein fragment that may be a key factor in damaging cell-to-cell communication and causing the loss of brain cells in Alzheimer's disease.

For this study, Dr. Keller's team will test the hypothesis that HDAC inhibitors suppress the toxic effect of beta-amyloid by increasing the production of specific proteins. Results of this work should lead to a better understanding of early pathological events in Alzheimer's and suggest new lines of investi-gation for novel treatments.