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 language | English (US) |
---|---|
Pages (from-to) | 2931-2947 |
Number of pages | 17 |
Journal | Journal of Molecular Biology |
Volume | 427 |
Issue number | 18 |
DOIs | |
State | Published - Sep 11 2015 |
Funding
This work was supported by the National Institutes of Health (National Institute on Aging, National Institute of General Medical Sciences, and National Institute of Mental Health), the Chicago Biomedical Consortium , the Ellison Medical Foundation , and the Daniel F. and Ada L. Rice Foundation . We would like to thank Dr. Johnathan Labbadia for thoughtful comments on the manuscript.
Keywords
- Abbreviations CFTR cystic fibrosis transmembrane conductance regulator
- PN proteostasis network
- TPR tetratricopeptide repeat
ASJC Scopus subject areas
- Biophysics
- Structural Biology
- Molecular Biology