Protein homeostasis (proteostasis) refers to the cellular state in which proteins and protein complexes are generated and functionally maintained at the right time and place within a cell. This process is managed by a network of molecular components and machines that monitor protein function in a spatial and temporal manner, from their biogenesis on ribosomes, trafficking to the correct cellular location, folding, assembly, post-translational modification, and finally, as required, their removal by proteolytic systems. At any given time, the integrity of the proteome is dependent on the relative success of each step in this process, which is contingent not only on the cellular environment but also on the availability of active components of the proteostasis network (PN). Under unfavourable conditions, following collapse of the PN (e.g. under conditions of prolonged stress), protein misfolding ensues resulting in aborted protein assembly and the appearance of non-native protein aggregates. The accumulation of these protein aggregates is a hallmark of aging and various neurodegenerative diseases.
The aim of this Research Topic is to highlight the role of the PN as guardians of eukaryotic cells. The Research Topic will focus on two major PN systems that protect the cell from protein conformational diseases, namely, the Hsp70 and Hsp40 chaperones that are responsible for rescue and recovery of non-native or misfolded proteins, and the AAA+ (ATPases associated with a variety of cellular activities) protease that are responsible for the removal of harmful or unwanted proteins. Over the past few years there have been a number of significant developments in this area of proteostasis research that have not only advanced our structural and functional understanding of these systems, but also underscored the physiological importance of these systems in protecting the cell from protein conformational disease. This Research Topic will feature critical reviews that examine the major developments that have been made within the field, and original research that further extends our understanding of these systems and their significance in human health, disease and aging.
Areas to be covered by this research topic may include, but are not limited to:
• The mechanism of action of specific chaperone and proteolytic systems.
• How these protein systems interact with specific substrates to prevent protein misfolding and hence aggregation.
• The potential therapeutic use of chaperones, proteases and specific inhibitors to regulate, restrict or eliminate protein aggregates from the cell.
Collectively, these topics aim to provide a comprehensive understanding of the strategies used by different PN systems and how the cell, as a whole, tries to adapt to counteract the toxic effects of protein misfolding.
Protein homeostasis (proteostasis) refers to the cellular state in which proteins and protein complexes are generated and functionally maintained at the right time and place within a cell. This process is managed by a network of molecular components and machines that monitor protein function in a spatial and temporal manner, from their biogenesis on ribosomes, trafficking to the correct cellular location, folding, assembly, post-translational modification, and finally, as required, their removal by proteolytic systems. At any given time, the integrity of the proteome is dependent on the relative success of each step in this process, which is contingent not only on the cellular environment but also on the availability of active components of the proteostasis network (PN). Under unfavourable conditions, following collapse of the PN (e.g. under conditions of prolonged stress), protein misfolding ensues resulting in aborted protein assembly and the appearance of non-native protein aggregates. The accumulation of these protein aggregates is a hallmark of aging and various neurodegenerative diseases.
The aim of this Research Topic is to highlight the role of the PN as guardians of eukaryotic cells. The Research Topic will focus on two major PN systems that protect the cell from protein conformational diseases, namely, the Hsp70 and Hsp40 chaperones that are responsible for rescue and recovery of non-native or misfolded proteins, and the AAA+ (ATPases associated with a variety of cellular activities) protease that are responsible for the removal of harmful or unwanted proteins. Over the past few years there have been a number of significant developments in this area of proteostasis research that have not only advanced our structural and functional understanding of these systems, but also underscored the physiological importance of these systems in protecting the cell from protein conformational disease. This Research Topic will feature critical reviews that examine the major developments that have been made within the field, and original research that further extends our understanding of these systems and their significance in human health, disease and aging.
Areas to be covered by this research topic may include, but are not limited to:
• The mechanism of action of specific chaperone and proteolytic systems.
• How these protein systems interact with specific substrates to prevent protein misfolding and hence aggregation.
• The potential therapeutic use of chaperones, proteases and specific inhibitors to regulate, restrict or eliminate protein aggregates from the cell.
Collectively, these topics aim to provide a comprehensive understanding of the strategies used by different PN systems and how the cell, as a whole, tries to adapt to counteract the toxic effects of protein misfolding.
