Molecular chaperones, heat-shock proteins (HSPs), or stress proteins, are highly conserved proteins that have a critical role in the regulation of cellular protein homeostasis (proteostasis), essential for the maintenance of the functionality of the proteome and, ultimately, of cells. Disruption of proteostasis leads to aberrantly folded proteins that typically lose their function. The accumulation of misfolded and aggregated proteins, due to genetic mutations or an age-related decline, is also cytotoxic and has been linked to the pathogenesis of neurodegenerative diseases, such as Alzheimer’s, Parkinson’s, Huntington’s and prion diseases, or amyotrophic lateral sclerosis (ALS).
In addition to essential roles in de novo protein folding and the refolding of misfolded proteins, molecular chaperones are functionally diverse and participate in a myriad of cellular processes. These functions include preventing or resolving protein aggregation, or regulating proteostasis through fundamental processes such as the unfolding protein response (UPR), chaperone-mediated autophagy (CMA), and the ubiquitin-proteasome system (UPS). Chaperones are important components of cellular networks, as they form functional complexes with each other, with numerous co-chaperones that regulate their function and with hundreds of client cellular proteins. Therefore, they promote the crosstalk between various signalling pathways and regulate transcriptional networks. Furthermore, certain stress proteins have been found to display diverse immune abilities and to have a significant role in immunity.
In this Research Topic, we will focus on the role of molecular chaperones in neurodegeneration as well as in biochemical or biological processes which may lead to neurodegeration, providing a comprehensive overview of the most recent findings, advances, and implications as putative targets for therapeutic intervention.
Molecular chaperones, heat-shock proteins (HSPs), or stress proteins, are highly conserved proteins that have a critical role in the regulation of cellular protein homeostasis (proteostasis), essential for the maintenance of the functionality of the proteome and, ultimately, of cells. Disruption of proteostasis leads to aberrantly folded proteins that typically lose their function. The accumulation of misfolded and aggregated proteins, due to genetic mutations or an age-related decline, is also cytotoxic and has been linked to the pathogenesis of neurodegenerative diseases, such as Alzheimer’s, Parkinson’s, Huntington’s and prion diseases, or amyotrophic lateral sclerosis (ALS).
In addition to essential roles in de novo protein folding and the refolding of misfolded proteins, molecular chaperones are functionally diverse and participate in a myriad of cellular processes. These functions include preventing or resolving protein aggregation, or regulating proteostasis through fundamental processes such as the unfolding protein response (UPR), chaperone-mediated autophagy (CMA), and the ubiquitin-proteasome system (UPS). Chaperones are important components of cellular networks, as they form functional complexes with each other, with numerous co-chaperones that regulate their function and with hundreds of client cellular proteins. Therefore, they promote the crosstalk between various signalling pathways and regulate transcriptional networks. Furthermore, certain stress proteins have been found to display diverse immune abilities and to have a significant role in immunity.
In this Research Topic, we will focus on the role of molecular chaperones in neurodegeneration as well as in biochemical or biological processes which may lead to neurodegeration, providing a comprehensive overview of the most recent findings, advances, and implications as putative targets for therapeutic intervention.
