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2007 Grant - Leissring
Genetic Modulation of Beta-Amyloid Catabolism
Malcolm A. Leissring, Ph.D.
Scripps Research Institute
2007 Investigator-Initiated Research Grant
Beta-amyloid is a protein fragment that is the main constituent of amyloid plaques, a characteristic feature of Alzheimer pathology. Because it is toxic to nerve cells, many studies have focused on ways to reduce the production of beta-amyloid or to remove it efficiently from the brain. To date, most research has focused on the mechanisms involved in the production of beta-amyloid. Much less is known about its removal or destruction (catabolism).
Malcolm A. Leissring, Ph.D., and colleagues plan to use large-scale screening methods to identify naturally occurring enzymes that degrade beta-amyloid. This method involves systematically increasing the expression of genes in living cells and then testing whether the products of those genes (proteins) are enzymes that catabolize beta-amyloid. This method has been used to identify genes and proteins involved in the production of beta-amyloid, so it is likely to be successful in identifying genes and proteins involved in its catabolism.
If Dr. Leissring can identify these proteins, it may be possible that their expression could be increased so that beta-amyloid is removed from the brain, thereby preventing the development of new amyloid plaques. In this way, these studies may help to identify targets for new therapeutic approaches for the treatment of Alzheimer's disease.