The Biology of Proteostasis in Aging and Disease

2015/03/18 by Johnathan Labbadia, Richard I Morimoto, Richard I. Morimoto · 1,522 citations
Biochemistry, Genetics and Molecular Biology · Medicine · #Bioinformatics #Biology #Cell biology #Computational biology #Context (archaeology) #Disease #Endoplasmic Reticulum Stress and Disease #Genetics, Aging, and Longevity in Model Organisms #Medicine #Pathology #Protein aggregation #Protein folding #Proteome #Proteostasis #Ubiquitin and proteasome pathways

paper · pdf · doi:10.1146/annurev-biochem-060614-033955

published in Annual Review of Biochemistry 84(1), 435-464 (Annual Reviews)

openalex publication_date 2015/03/18 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/05

Abstract

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.

Citations

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