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2010 Grants - Hengst
The Role of Intra-Axonal Protein Synthesis in Alzheimer's Disease
Ulrich Hengst, Ph.D.
Columbia University Medical Center
New York, New York
2010 New Investigator Research Grant
Alzheimer's disease is characterized by accumulations in the brain of beta-amyloid, a protein fragment, and abnormal tau protein. According to current research, neurons that suffer beta-amyloid or tau build-up possess increased levels of molecules that promote the translation of proteins from genes. These studies, however, have focused on protein-making events that occur throughout the entire cell. Some researchers have begun focusing on protein translation that occurs in specific areas of the cell called the axons. Axons are armlike structures that help transport nutrients and other compounds to various cellular compartments.
Ulrich Hengst, Ph.D., and colleagues have observed that the messenger ribonucleic acid (mRNA) for tau is located on nerve cell axons. mRNA is a kind genetic "photocopy" that the cell uses to make proteins from genes. The appearance of tau mRNA on axons suggests that the production of certain Alzheimer-related proteins may be localized in these cellular structures.
For their proposed grant, Dr. Hengst and colleagues will develop cultured nerve cells in tiny, fluid-filled chambers that are not much larger than the cells themselves. This technique will facilitate the study of minute chemical reactions in the cells' axons. The researchers will then treat their cells with beta amyloid. Subsequent analysis will determine 1) whether such treatment alters the production of tau and other cellular proteins from genes and 2) whether these alterations lead to Alzheimer pathology.
The results of Dr. Hengst's effort could clarify how and where Alzheimer-related proteins accumulate in cells. The work could also lead to novel disease treatments that focus on blocking abnormal protein translation.