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Research Grants - 2005


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Research Grants 2005


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2005 Grant - Gong

O-GlcNAcylation and Phosphorylation of Tau protein

Cheng-Xin Gong, M.D.
Research Foundation for Mental Hygiene, Inc.
New York State Institute for Basic Research
Staten Island, New York

2005 Investigator-Initiated Research Grant

Neurofibrillary tangles are a key feature of Alzheimer's disease. Tangles are largely composed of abnormal tau, proteins which normally play a role in stabilizing the structural framework and transport system of nerve cells. Tau normally undergoes a chemical change that adds phosphate groups to the protein, a process called phosphorylation. Tau proteins in tangles have an abnormally large number of phosphate groups that appear to alter the protein's structure and function and may lead to the formation of tangles. The biochem-ical mechanisms that direct both normal and abnormal phosphorylation are not well understood.

Cheng-Xin Gong, M.D., and colleagues recently found that tau proteins are modified by a biochemical process called O-GlcNAcylation by which certain sugar molecules direct other chemical "remodeling." These findings suggest the possibility that O-GlcNAcylation may regulate the phosphate content of tau. Therefore, aberrations in O-GlcNAcylation may be involved in the eventual formation of tangles.

The objective of Dr. Gong's research project is to characterize the nature and functions of O-GlcNAcylation as it relates to tau and its potential role in the abnormal phosphorylation of tau in the Alzheimer brain. Completion of this project may provide new insight into the origins of tangles and may help the development of new therapeutic strategies.