Shaping proteostasis at the cellular, tissue, and organismal level.
TLDR
This review by Morimoto and colleagues examines mechanisms by which protein homeostasis (proteostasis) is achieved in multicellular organisms and discusses the implications for health and disease.Abstract:
The proteostasis network (PN) regulates protein synthesis, folding, transport, and degradation to maintain proteome integrity and limit the accumulation of protein aggregates, a hallmark of aging and degenerative diseases. In multicellular organisms, the PN is regulated at the cellular, tissue, and systemic level to ensure organismal health and longevity. Here we review these three layers of PN regulation and examine how they collectively maintain cellular homeostasis, achieve cell type-specific proteomes, and coordinate proteostasis across tissues. A precise understanding of these layers of control has important implications for organismal health and could offer new therapeutic approaches for neurodegenerative diseases and other chronic disorders related to PN dysfunction.read more
Citations
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The proteostasis network and its decline in ageing.
TL;DR: The possibilities of pharmacological augmentation of the capacity of proteostasis networks hold great promise for delaying the onset of age-related pathologies associated with proteome deterioration and for extending healthspan.
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Pathways of cellular proteostasis in aging and disease.
TL;DR: Klaips et al. outline the pathways and molecular mechanisms of cellular protein homeostasis, or protestasis, and discuss how a decline in proteostasis during aging contributes to disease.
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Aging, inflammation and the environment
TL;DR: It is pointed out that longitudinal studies with a life course approach are needed to gain further mechanistic insight on the processes that lead to functional decline with aging, and the role played by inflammation and environmental challenges.
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Alzheimer’s Disease: From Firing Instability to Homeostasis Network Collapse
Samuel Frere,Inna Slutsky +1 more
TL;DR: It is hypothesized that firing instability and impaired synaptic plasticity at early AD stages trigger a vicious cycle, leading to dysregulation of the whole IHN, and represents the major driving force of the transition from early memory impairments to neurodegeneration.
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Functional Modules of the Proteostasis Network
TL;DR: The capacity and limitations of the PN in maintaining proteome integrity in the face of proteotoxic stresses, such as aggregate formation in neurodegenerative diseases are discussed.
References
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Zarah Batulan,Gayle A. Shinder,Sandra Minotti,Bei Ping He,Mohammad M. Doroudchi,Josephine Nalbantoglu,Michael J. Strong,Heather D. Durham +7 more
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TL;DR: The current understanding of the mechanisms implicated in the formation of protein aggregates in the endocrine pancreas and associated toxicity in the light of the long-standing knowledge from neurodegenerative disorders associated with protein misfolding is discussed.
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Evan T. Powers,William E. Balch +1 more
TL;DR: Proteostasis networks have co-evolved with the proteome to regulate the physiological state of the cell, reflecting the unique stresses that different cells or organisms experience, and that they have a key role in driving evolution by closely managing the link between the phenotype and the genotype.