2007 Grant - Arancio

CBP Involvement in Alzheimer's Disease and Its Potential Therapeutic Value

Ottavia Arancio, M.D.
Columbia University
New York, New York

Candidate for 2007 Zenith Fellows Award

CREB and CREB-binding protein (CBP) are two proteins inside the nucleus of nerve cells. The two proteins work together to allow the expression of genes necessary for memory formation. CREB binds to specific regions of DNA to promote the production of proteins. CBP prepares the DNA for binding of CREB by chemically modifying other proteins known as histones, which are housekeeping proteins that maintain the long strands of DNA in an orderly arrangement.

Dysfunction of CREB and CBP have been implicated in Alzheimer's disease and other nervous system disorders. For example, the activity of CREB is reduced by beta-amyloid, a protein fragment that is a key suspect in Alzheimer pathology. Dysfunction of CBP causes several neurological disorders leading to abnormal function of the brain.

Dr. Ottavio Arancio, M.D., and colleagues have planned a series of experiments to study the role of CBP in Alzheimer's disease. In the mouse model of Alzheimer's disease that the investigators plan to use, modification of histones by CBP is reduced because of a dysfunction in the activity of CBP. The investigators plan to reverse this effect by increasing the modification of histones. They will then look to see if this action leads to improvements in brain function in the mice.

Specific drugs are known to enhance the modification of histones by CBP. The research conducted by Dr. Arancio and colleagues will help to determine if such drugs are useful therapies for Alzheimer's disease.