Development of a genetic approach to study insulin-degrading enzyme in yeast
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The Insulin-Degrading Enzyme (IDE) is a metalloprotease known for cleaving insulin and the neurotoxic amyloid beta peptide in humans. Because of these properties, IDE has been thought as having potential therapeutic value in Alzheimer disease. IDE has significant homology to yeast enzymes, Axl1p and Ste23p, which are important for production of the yeast a-factor mating pheromone. We have determined that yeast-expressed IDE can produce a-factor in vivo and cleave insulin in vitro. Accordingly, we conclude that IDE can be functionally expressed in yeast and propose that yeast can be used as a tractable model system to study the enzymatic function of IDE. This research aims to define the enzymatic properties of IDE, which could eventually lead to improved therapeutic approaches for the treatment of Alzheimer disease.