Can I read Pathogenic mechanisms - A27 Targeting glutamine dehydrogenase activity to induce autophagy and ameliorate neuronal degeneration; studies using a drosophila model for huntington’ disease on EtoBox?

Pathogenic mechanisms - A27 Targeting glutamine dehydrogenase activity to induce autophagy and ameliorate neuronal degeneration; studies using a drosophila model for huntington’ disease by Bellosta, Paola; Paiardi, Chiara; Pasini, Maria E is a scholarly article available to read on EtoBox.

What is Pathogenic mechanisms - A27 Targeting glutamine dehydrogenase activity to induce autophagy and ameliorate neuronal degeneration; studies using a drosophila model for huntington’ disease about?

mouse models with calpastatin knockout mice to assess its effect not only on huntingtin cleavage and aggregation but also additional molecular markers. Methods Effects of depleting the endogenous inhibitor of calpains on huntingtin fragmentation and aggregation, as well as on other molecular markers of Huntington disease were investigated via western blotting, filter retardation assays and immunocytochemistry or immunohistochemistry. Results We demonstrated that reduced or ablated calpastatin expression triggers calpain overactivation and a consequently increased mutant huntingtin cleavage in cells and in vivo. These alterations were accompanied by an elevated formation of predominantly cytoplasmic huntingtin aggregates. Conversely, calpastatin overexpression in cells attenuated huntingtin fragmentation and aggregation. In addition, we observed an enhanced cleavage of DARPP-32, p35 and synapsin-1 in neuronal tissue upon calpain overactivation. Conclusions Our results corroborate the important role of calpains in the molecular pathogenesis of Huntington disease and endorse targeting these proteolytic enzymes as a therapeutic approach.

Author

Bellosta, Paola; Paiardi, Chiara; Pasini, Maria E

Publisher

BMJ Publishing Group Ltd

Published

2018

Language

EN