The disruption of proteostasis in neurodegenerative diseases

Cells count on surveillance systems to monitor and protect the cellular proteome which, besides being highly heterogeneous, is constantly being challenged by intrinsic and environmental factors. In this context, the proteostasis network (PN) is essential to achieve a stable and functional proteome. Disruption of the PN is associated with aging and can lead to and/or potentiate the occurrence of many neurodegenerative diseases (ND). This not only emphasizes the importance of the PN in health span and aging but also how its modulation can be a potential target for intervention and treatment of human diseases.info:eu-repo/semantics/publishedVersio

EDITORIAL

The ubiquitin-proteasome system has emerged in the last decades as a new paradigm in cell physiology. Ubiquitin is found in fundamental levels of cell regulation, as a target for degradation to the proteasome or as a signal that controls protein function in a complex manner. Even though many aspects of the ubiquitin system remain unexplored, the contributions on the field uncover that ubiquitin represents one of the most sophisticated codes in cellular biology. The proteasome is an ATP-dependent protease that degrades a large number of protein substrates in the cell. The proteasome recruits substrates by a number of receptors that interact with polyubiquitin. Recently, it has been shown that one of these receptors, Rpn10, is regulated by monoubiquitination. In this chapter, we show an overview of the central aspects of the pathway and describe the methodology to characterize in vitro the monoubiquitination of proteasome subunits. © 2012 Springer Science+Business Media New York.Peer Reviewe