To view an abstract, select an author from the vertical list on the left.
2010 Grants - McIntire
Dissecting the Role of PI3K Family Members in Aβ Biogenesis
Laura Beth McIntire, Ph.D.
Columbia University Medical Center
New York, New York
2010 New Investigator Research Grant
Alzheimer's disease is characterized by brain accumulations of the protein fragment beta-amyloid. This fragment is thought to disrupt cell-to-cell communication in the brain and cause brain cell death. Many researchers have been looking for compounds that can inhibit the production of harmful beta-amyloid, and possibly slow or prevent Alzheimer progression.
Certain compounds called phosphatidylinositol 3-kinases (PI3Ks) have been shown to promote amyloid build-up in cells and in mice engineered to develop Alzheimer-like symptoms. Yet scientists have not found the specific PI3K family member that most affects beta-amyloid production. Nor have they determined the biological mechanisms underlying this PI3K-amyloid relationship. In preliminary studies, Laura Beth McIntire, Ph.D., and colleagues have identified a compound that inhibits beta-amyloid production in cultured cells. This compound is known to block the activity of a protein called ataxia telangiectasia mutated kinase (ATM), which belongs to a PI3K-related family called PI3K-like kinases (PIKKs).
For their proposed effort, Dr. McIntyre and colleagues will inhibit the activities of several PI3K and PIKK family members in cultured cells. They hope to determine whether ATM or another kinase is most responsible for regulating beta-amyloid production. After determining the most promising example, the team will test whether inhibiting this compound can prevent beta-amyloid accumulation in Alzheimer-like mice.
The results of Dr. McIntyre's study will help clarify how beta-amyloid accumulates in Alzheimer's disease. The work may also identify a novel drug treatment for the disease.