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2005 Grant - Dineley
NF-kB Signaling Axis as a Target in Alzheimer's Disease Therapy
Kelly Dineley, M.S., Ph.D.
University of Texas Medical Branch
2005 New Investigator Research Grant
Though it is widely believed that there is an inextricable link between Alzheimer's disease pathology and inflammation, the precise relationship between the two is poorly understood. One possible connection is beta-amyloid, a protein fragment that accumulates in the brains of people with Alzheimer's and that may stimulate production of molecules that cause inflammation.
Kelly Dineley, Ph.D., and colleagues will test this idea, focusing specifically on a molecule called NF-kappaB. Though this protein is elevated in many chronic inflammatory diseases, the effect of beta-amyloid on NF-kappaB has not been explored.
To test the relationship between the two proteins, the researchers will use genetically altered mice that produce large amounts of beta-amyloid and develop an Alzheimer-like pathology. They will follow these animals over time, measuring to see if increases in beta-amyloid in the brain coincide with any changes in the level of NF-kappaB or other molecules that interact with it. In particular, the researchers will focus on the hippocampus, an area of the brain that is badly affected in Alzheimer's disease.
Dineley and colleagues will also treat the genetically altered mice with drug-like molecules that may slow or prevent the cognitive decline that results from Alzheimer's. These treatments will include novel NF-kappaB inhibitors. This two-pronged approach could reveal both new drugs and new drug targets that could prove important in the fight against Alzheimer's disease.