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2012 Grants - Lee
Fyn in Tau-Induced Neurodegeneration
Gloria Lee, Ph.D.
University of Iowa
Iowa City, Iowa
2012 Investigator-Initiated Research Grant
Tau is a protein found in the brain. When tau becomes abnormally modified by addition of phosphate chemical groups (phosphorylation), it forms neurofibrillary tangles, one of the hallmark features of mechanisms in the brain associated with Alzheimer's disease. One of the enzymes that performs phosphorylation of tau is Fyn; there is evidence that some individuals with Alzheimer's disease have genetic changes of Fyn that cause excessive phosphorylation of tau.
Gloria Lee, Ph.D., and colleagues have proposed to study the role of Fyn in tau phosphorylation, and subsequent development of neurofibrillary tangles and the cell death or neurodegeneration seen in brain disease like Alzheimer's disease. They plan to conduct these studies using mice that have been genetically engineered to have mutations that increase their susceptibility to Fyn-induced phosphorylation. These animals exhibit Alzheimer's-like neurodegeneration in the brain. The researchers will then induce other genetic changes that block Fyn and study whether those changes prevent neurodegeneration and the resulting brain dysfunction. These studies will address the question of whether drugs to block Fyn are candidate drugs to slow or prevent progression of Alzheimer's disease.