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The Biology of Proteostasis in Aging and Disease
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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.
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“Aging affects all organ systems through common underlying mechanisms such as changes in the immune system, oxidative stress, and DNA damage and replication errors, as well as epigenetic changes and accumulation of abnormal proteins across multiple organ systems.35–38”
From Defining Optimal Brain Health in Adults: A Presidential Advisory From the American Heart Association/American Stroke Association (2017) · cites this paper as [38]
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Metadata
- Authors
- Labbadia, J., & Morimoto, R. I.
- Affiliations
- Department of Molecular Biosciences, Rice Institute for Biomedical Research, Northwestern University, Evanston, Illinois 60208;
- Northwestern University (US)
- Corresponding author
- Morimoto, Richard I
- ORCID
- Morimoto, Richard I
- Venue
- Annual Review of Biochemistry
- Publisher
- Annual Reviews
- Published
- 2015-06-02
- Volume
- 84
- Issue
- 1
- Pages
- 435-464
- ISSN
- 0066-4154 (ISSN-L)
- 1545-4509
- PMC
- PMC4539002
- OpenAlex
- W2152231829
- Cited by
- 1,472
- References
- 182
- Citations by year
- 2026: 142 · 2025: 127 · 2024: 150 · 2023: 152 · 2022: 140 · 2021: 148 · 2020: 143 · 2019: 139 · 2018: 136 · 2017: 106 · 2016: 69 · 2015: 19
- FWCI
- 10.55
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Annual Review of Biochemistry (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- Ellison Medical Foundation
- National Institutes of Health (5p50mh094267-05)
- National Institute on Aging (R37AG026647, R01AG026647)
- National Institute of Mental Health (P50-MH094267)
- National Institute of General Medical Sciences (P50GM081892, R01GM038109, R37GM038109)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Keywords
- proteostasis, proteostasis network, aging, protein aggregation, stress response pathways, protein conformational diseases, disease susceptibility, lifespan
- MeSH terms
- Aging, Animals, Humans, Proteins, Neurodegenerative Diseases, Metabolic Networks and Pathways, Proteolysis, Endoplasmic Reticulum Stress
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