Interaction studies of Insulin Degrading Enzyme (IDE) with a model membrane

Abstract

Alzheimer’s disease is a progressive neurodegenerative disease. A hall mark of AD is accumulation of Aβ peptide. Insulin degrading enzyme IDE has a key role in degrading Aβ intracellularly and extracellularly. It is a zinc metalloendopeptidase and it degrades a wide range of substrates include insulin, amylin, insulin-like growth factors. Cholesterol is an essential component of mammalian bilayer’s function and organization. Because of its structure, it can increase the order within the membrane and hence affects membrane fluidity. Although cholesterol has shown modulating effect on IDE by upregulation of its activity, level, stability and gene expression. However, binding between cholesterol and IDE need to be considered. First, binding has been investigated by co-immunoprecipitation and mass spectrometry technique, then were studied with the Langmuir film balance technique. Finally, molecular modelling has been employed with the swissdock. Recombinant human IDE was incubated with cholesterol and co-immunoprecipitated and fed to mass spectrometer to detect the interaction. However, results showed no binding detected. In line with this result, in-silico study and Langmuir monolayer assay showed that IDE did not destroy the model membrane.