Topic
Proteotoxicity
About: Proteotoxicity is a research topic. Over the lifetime, 549 publications have been published within this topic receiving 23151 citations.
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TL;DR: The co-chaperone Cdc37 can regulate aspects of tau pathogenesis in two ways: by directly stabilizing it via Hsp90 and by regulating the stability of distinct tau kinases.
58 citations
TL;DR: Recent evidence that C. elegans has mechanisms to transmit certain classes of toxic proteins between tissues and a complex stress response that integrates and coordinates signals from single cells and tissues across the organism is focused on.
Abstract: Caenorhabditis elegans has a number of distinct advantages that are useful for understanding the basis for cellular and organismal dysfunction underlying age-associated diseases of protein misfolding. Although protein aggregation, a key feature of human neurodegenerative diseases, has been typically explored in vivo at the single-cell level using cells in culture, there is now increasing evidence that proteotoxicity has a non-cell-autonomous component and is communicated between cells and tissues in a multicellular organism. These discoveries have opened up new avenues for the use of C. elegans as an ideal animal model system to study non-cell-autonomous proteotoxicity, prion-like propagation of aggregation-prone proteins, and the organismal regulation of stress responses and proteostasis. This Review focuses on recent evidence that C. elegans has mechanisms to transmit certain classes of toxic proteins between tissues and a complex stress response that integrates and coordinates signals from single cells and tissues across the organism. These findings emphasize the potential of C. elegans to provide insights into non-cell-autonomous proteotoxic mechanisms underlying age-related protein-misfolding diseases.
58 citations
TL;DR: Some recent advances in understanding of how misfolded proteins can injure and are handled in the cell are highlighted, examining the emerging evidence for targeting proteotoxicity as a new therapeutic strategy for heart disease.
57 citations
TL;DR: This relatively new role of chaperones in mediating selective autophagy is reviewed and how alterations of this function can lead to human pathologies associated to proteotoxicity is commented on.
57 citations
TL;DR: The data support a model where the genes Sxl in Drosophila, sdc-2 in Caenorhabditis elegans, and Xist in mammals regulate mitochondrial maintenance across generations and in aging, and suggest that metazoan life span interventions may act through a common hormesis mechanism involving liver UPRmt, mitochondrial maintenance and sexual differentiation.
56 citations