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2011 Grants - Zhu
Role of EphB2 Signal in Tau Pathology in Alzheimer's Disease
Ling-Qiang Zhu, Ph.D.. M.D.
Huazhong University of Science and Technology
2011 New Investigator Research Grant
The protein tau normally plays an important role in maintaining the structure of brain cells. Tau is modified by a process called phosphorylation, or the addition of phosphate molecules. In Alzheimer's disease, however, tau becomes excessively phosphorylated and loses the ability to carry out its normal functions. Such hyperphosphorylated tau tends to accumulate in the brain into neurofibrillary tangles, a key hallmark of Alzheimer's disease. Neurofibrillary tangles have been shown to disrupt communication between brain cells and cause cognitive decline. Yet despite the well-known effects of abnormal tau, scientists have not yet clearly defined the mechanisms that initiate tau pathologies or brain changes.
Ling-Qiang Zhu, Ph.D., M.D., and colleagues have been studying a particular receptor, or cellular "docking site," that may be involved in abnormal tau production. The Ephrin type-B receptor 2 (EphB2) is one of a group of receptors associated with the development of structures in the nervous system. Previous studies have also shown that in people with early Alzheimer's disease, levels of EphB2 decrease in the hippocampus, an area of the brain associated with learning and memory. In preliminary research, Dr. Zhu's group found that by eliminating EphB2 in cultured brain cells, they could induce hyperphosphorylation of tau. Moreover, the team was able to prevent hyperphosphorylation in the cells by overexpressing EphB2.
For this grant, Dr. Zhu and colleagues will conduct a larger study of the role of EphB2 in neurofibrillary tangle development. Using cultured cells, they hope to identify how changes in EphB2 signaling during Alzheimer's may initiate the process of hyperphosphorylation and hasten the process of tau pathology. They will also explore different ways of boosting EphB2 activity to prevent such pathology. The results of their efforts could lead to novel therapies for treating Alzheimer's disease and other cognitive disorders involving tau.