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Research Grants 2005


To view an abstract, select an author from the vertical list on the left side.

2005 Grant - Hartley

Transglutaminase's Role in Neurodegeneration

Dean M. Hartley, Ph.D.
Brigham and Women's Hospital
Cambridge, Massachusetts

2005 Investigator-Initiated Research Grant

A key feature of Alzheimer's disease pathology is the aggregation, or clumping together, of beta-amyloid, a tiny protein fragment. A leading hypothesis in Alzheimer's research is that some aggregated form of beta-amyloid may cause the breakdown of cell-to-cell communication and the loss of cells in the brain. The mechanism by which aggregation occurs has not been completely characterized.

In preliminary findings, Dean Hartley, Ph.D., and colleagues found that beta-amyloid aggregation may occur through an interaction between the protein fragment and an enzyme called transglutaminase (TGase). TGase appears modify beta-amyloid in a manner that results in crosslinking, or the creation of highly stable bonds, between beta-amyloid molecules. The researchers hypothesize that it is this crosslinking that results in the formation of beta-amyloid aggregates.

To test this hypothesis, Dr. Hartley's group will (1) examine and characterize the properties of crosslinked beta-amyloid molecules in cultured cells and from cells of genetically altered mice that develop an Alzheimer-like disorder, (2) determine if TGase-mediated crosslinking enhances the stability of beta-amyloid aggregation and beta-amyloid's resistance to breaking down and
(3) examine the potential toxic effect of TGase-crosslinked beta-amyloid aggregates on nerve cells.

The findings may clarify key disease processes and suggest targets for future development of disease-modifying therapies.