The aetiology of Alzheimer Disease (AD) and diabetes mellitus type 2 (DM) remains unknown and genetic factors can explain only a small percentage of cases. However, metal ions such as copper and zinc are known to play an important role in many biomolecular processes and their dyshomeostasis has been considered a critical factor in the development of AD and DM. Furthermore, accumulating evidence correlates insulin dysmetabolism with dementia-linked brain plaques and IDE (insulin-degrading enzyme) has been observed to degrade both Aβ peptides and insulin. For this reason, an altered activity of IDE has been proposed as a possible factor bridging AD and DM pathogenesis. Therefore, the therapeutic potentials offered by the ability to regulate the activity of IDE are thought to be highly promising. In an attempt to unveil some of the molecular determinants lying at the root of AD and DM and inspired by all these issues, we have focused on the effects that metal ions may have on the activity of IDE [1-2]. In particular, we have investigated the activity of IDE in different experimental conditions towards various substrates, including ubiquitin and polyubiquitin chains. Our results allowed us to gain insights in the role played by copper and zinc in modulating IDE activity and, in turn, in the regulation of the cross-talk between different cellular proteolytic pathways. References  G. Grasso, A. Pietropaolo, G. Spoto, G. Pappalardo, G. R. Tundo, C. Ciaccio, M. Coletta, E. Rizzarelli, Chemistry-A European Journal 2011, 17, 2752-2762.  G. Grasso, E. Rizzarelli, G. Spoto, J Mass Spectrom 2009, 44, 735-741.
|Titolo:||THE INFLUENCE OF METALLOSTASIS ON INSULIN-DEGRADING ENZYME ACTIVITY|
|Data di pubblicazione:||2011|
|Appare nelle tipologie:||4.1 Contributo in Atti di convegno|