The Biology of Proteostasis in Aging and Disease

By Johnathan Labbadia, Richard I. Morimoto. Annual Review of Biochemistry, 2015

1,312 citations recorded by the source corpus.

Loss of protein homeostasis (proteostasis) is a common feature of aging and disease that is characterized by the appearance of nonnative protein aggregates in various tissues. Protein aggregation is routinely suppressed by the proteostasis network (PN), a collection of macromolecular machines that operate in diverse ways to maintain proteome integrity across subcellular compartments and between tissues to ensure a healthy life span. Here, we review the composition, function, and organizational properties of the PN in the context of individual cells and entire organisms and discuss the mechanisms by which disruption of the PN, and related stress response pathways, contributes to the initiation and progression of disease. We explore emerging evidence that disease susceptibility arises from early changes in the composition and activity of the PN and propose that a more complete understanding of the temporal and spatial properties of the PN will enhance our ability to develop effective treatments for protein conformational diseases.

Subfields: Aging, Cell Biology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/da0a477baa996d58ca08ef327a994178c9d58fc0

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Citations in the corpus

Metabolic Control of Longevity. (2016, background): “Loss of Proteostasis Aging and various aging-associated diseases are associated with impaired proteostasis (protein homeostasis) (Labbadia and Morimoto, 2015).”
Protein Misfolding, Amyloid Formation, and Human Disease: A Summary of Progress Over the Last Decade. (2017, background): “There is also evidence that the age-related accumulation of protein aggregates is both an effect and a cause of proteostasis network decline, driving a vicious cycle that ultimately leads to its collapse (81, 196).”
The integrated stress response (2016, neutral): “During aging in the nematode Caenorhabditis elegans ( C. elegans ), the accumulation of neurotoxic protein aggregates may influence protein homeostasis (proteostasis) in somatic tissues [251].”
In vivo aspects of protein folding and quality control (2016, background): “Importantly, decline or disruption of the PN is strongly associated with aging and diseases of aberrant protein folding and aggregation (4, 126).”