The Chemical Biology of Molecular Chaperones - Implications for Modulation of Proteostasis

Kristoffer R. Brandvold, Richard I. Morimoto*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

57 Scopus citations

Abstract

Protein homeostasis (proteostasis) is inextricably tied to cellular health and organismal lifespan. Aging, exposure to physiological and environmental stress, and expression of mutant and metastable proteins can cause an imbalance in the protein-folding landscape, which results in the formation of non-native protein aggregates that challenge the capacity of the proteostasis network (PN), increasing the risk for diseases associated with misfolding, aggregation, and aberrant regulation of cell stress responses. Molecular chaperones have central roles in each of the arms of the PN (protein synthesis, folding, disaggregation, and degradation), leading to the proposal that modulation of chaperone function could have therapeutic benefits for the large and growing family of diseases of protein conformation including neurodegeneration, metabolic diseases, and cancer. In this review, we will discuss the current strategies used to tune the PN through targeting molecular chaperones and assess the potential of the chemical biology of proteostasis.

Original languageEnglish (US)
Pages (from-to)2931-2947
Number of pages17
JournalJournal of Molecular Biology
Volume427
Issue number18
DOIs
StatePublished - Sep 11 2015

Keywords

  • Abbreviations CFTR cystic fibrosis transmembrane conductance regulator
  • PN proteostasis network
  • TPR tetratricopeptide repeat

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

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