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Alzheimer's Disease And Developmental Biology Linked Through Single Molecule

Researchers at the University of Pennsylvania Medical Center and other institutions have uncovered a biochemical connection between presenilin, a molecule involved in the development of Alzheimer's disease, and another protein that controls crucial aspects of developmental biology. The findings are likely to lead to a new synergy between the two research areas and important advances in understanding on both fronts in the coming years. Reports on four related studies from the Penn team and three other groups will appear in the April 8 issue of Nature.

"The hope is that work in Alzheimer's disease will help inform people studying aspects of developmental biology about what might be going on in their neck of the woods and vice versa," says Mark E. Fortini, Ph.D., an assistant professor of genetics and senior author on one of the papers. "Once you find a common connection between two apparently disparate areas of biology, it can be very powerful in turning your eye on candidate ideas you may want to explore from the other discipline."

The scientists think that presenilin is involved in the processing of two proteins called Notch and amyloid precursor protein (APP). Mutations in the genes that codes for presenilin lead to misprocessing of Notch and APP so that the resulting proteins either cannot do their assigned jobs properly or actively damage cells. Problems with Notch disturb normal development in myriad ways and have even been implicated in one form of T-cell leukemia. Misprocessed APP is thought to produce the variant amyloid protein that dominates the plaques characteristic of Alzheimer's disease.

Notch, first discovered in fruit flies just before World War I, is involved in critical intercellular signaling in a wide array of development processes, many to do with the patterning of tissues. As the embryo develops, progenitor cells must differentiate from each other and take up different duties, a process that involv
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Contact: Franklin Hoke
hokef@mail.med.upenn.edu
215-662-2560
University of Pennsylvania School of Medicine
8-Apr-1999


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