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2007 Grant - Vosseller
Post-Translational Synaptic Proteomics and Function in Alzheimer's Disease
Keith Vosseller, Ph.D.
2007 New Investigator Research Grant
Synapses are specialized regions of nerve cells that allow the cells to send and receive rapid signals, thereby performing many of the unique functions of the brain. During the development of Alzheimer's disease, synapses often show very early signs of dysfunction, even before other pathological features of the disease appear.
Synaptic function requires the proper operation of numerous proteins. It has been observed that attached to many proteins at healthy synapses are chemical groups known as O-linked N-acetylglucosamine (O-GlcNAc). However, in the brains of people with Alzheimer's disease, O-GlcNAc levels are often much lower, sometimes being replaced by a different chemical group.
Keith Vosseller, Ph.D., and colleagues plan to study in detail how O-GlcNAc affects synaptic function using a mouse model that has been genetically altered to express many of the features of Alzheimer pathology. The researchers will use techniques that quantify the amount of O-GlcNAc on specific synaptic proteins during the development of Alzheimer-like pathology. They will also use drugs known to add or remove O-GlcNAc from proteins to determine how such changes affect synaptic function.
These studies may help to identify and characterize an important early event in the development of Alzheimer's disease. They may also help to identify potential new therapeutic strategies for altering the course of the disease.