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2011 Grants - Francis
The Involvement of Histone Acetyl-Transferases (HAT) in Alzheimer's Disease
Yitshak I. Francis, Ph.D.
Columbia University Medical Center
New York, New York
2011 New Investigator Research Grant
Histones are proteins that help maintain the organization of DNA, which is an essential nucleic acid in cells that contains specific genetic information needed for any living organism to develop and function. Histones have also been shown to regulate the expression of genes. They can be modified by a biochemical process called acetylation, or the addition of a group of atoms called the acetyl group. Enzymes called histone acetyl-transferases (HATs) help carry out acetylation, which have been shown to affect the brain's ability to form memories.
In preliminary research, Yitshak I. Francis, Ph.D., and colleagues have found that abnormal HAT activity may help produce a characteristic pathology or brain change of Alzheimer's disease. This pathology involves damage to synapses, or the channels through which brain cells send and receive chemical messages. Synaptic damage may also involve the protein fragment beta-amyloid, and it can hasten cognitive decline in Alzheimer's.
For this grant, Dr, Francis and colleagues will conduct research to expand on their earlier research. Using laboratory cells, they hope to show that increased brain levels of beta-amyloid induce changes in HAT activity that may be associated with synaptic damage. They also intend to determine whether increasing the expression and activity levels of HATs can prevent beta-amyloid-related damage to synapses and memory. The results of these efforts could lead to HAT-based therapies for slowing the progression of Alzheimer's disease and other neurological disorders linked to HAT deregulation — including Rubinstein-Taybi syndrome and Huntington's disease.