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2009 Grants - Arancio
Dysregulation of Histone Acetylation in Alzheimer's Disease
Ottavio Arancio, M.D.
New York, New York
2009 New Investigator Research Grant
Histones are proteins in close contact with the DNA in the nucleus of a cell. They function to maintain the organization of DNA, and recent studies have shown that histones regulate the expression of genes. Histones can be modified by biochemical processes such as addition or removal of acetyl groups, known as acetylation and deacetylation. Such modifications have been shown to control genetic mechanisms important for memory storage in brain cells.
Ottavio Arancio, M.D. and colleagues studied mice that had been genetically altered to exhibit Alzheimer-like pathology. They found that long-term potentiation—a cellular model of memory formation in the brain—was reduced by drugs that prevent deacetylation of histones. Furthermore, acetylation of histones in these animals was greatly reduced after a behavioral training session in comparison to normal mice. They have proposed to extend these studies to examine whether impairments in histone acetylation or deacetylation are involved in the memory impairment caused by beta-amyloid, a protein fragment in the brain implicated in the development of Alzheimer's disease.
For these studies, Dr. Arancio's team will use mice genetically altered to express excess beta-amyloid, and they will examine the biochemical pathways controlling histone acetylation. These experiments will improve our understanding of the biochemical mechanisms leading to memory impairment in Alzheimer's disease.