Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2022 Feb;21(2):115-140.
doi: 10.1038/s41573-021-00320-3. Epub 2021 Oct 26.

Pharmacological _targeting of endoplasmic reticulum stress in disease

Stefan J Marciniak  1 , Joseph E Chambers  2 , David Ron  2
Affiliations
Review

Pharmacological _targeting of endoplasmic reticulum stress in disease

Stefan J Marciniak et al. Nat Rev Drug Discov. 2022 Feb.

Abstract

The accumulation of misfolded proteins in the endoplasmic reticulum (ER) leads to ER stress, resulting in activation of the unfolded protein response (UPR) that aims to restore protein homeostasis. However, the UPR also plays an important pathological role in many diseases, including metabolic disorders, cancer and neurological disorders. Over the last decade, significant effort has been invested in _targeting signalling proteins involved in the UPR and an array of drug-like molecules is now available. However, these molecules have limitations, the understanding of which is crucial for their development into therapies. Here, we critically review the existing ER stress and UPR-directed drug-like molecules, highlighting both their value and their limitations.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Marciniak, S. J. & Ron, D. Endoplasmic reticulum stress signaling in disease. Physiol. Rev. 86, 1133–1149 (2006). - PubMed
    1. Ron, D. & Walter, P. Signal integration in the endoplasmic reticulum unfolded protein response. Nat. Rev. Mol. Cell Biol. 8, 519–529 (2007). - PubMed
    1. Mori, K., Ma, W., Gething, M. J. & Sambrook, J. A transmembrane protein with a cdc2+/CDC28-related kinase activity is required for signaling from the ER to the nucleus. Cell 74, 743–756 (1993). - PubMed
    1. Yoshida, H., Haze, K., Yanagi, H., Yura, T. & Mori, K. Identification of the cis-acting endoplasmic reticulum stress response element responsible for transcriptional induction of mammalian glucose-regulated proteins. Involvement of basic leucine zipper transcription factors. J. Biol. Chem. 273, 33741–33749 (1998). - PubMed
    1. Harding, H. P., Zhang, Y. & Ron, D. Protein translation and folding are coupled by an endoplasmic-reticulum-resident kinase. Nature 397, 271–274 (1999). - PubMed

MeSH terms

LinkOut - more resources

  NODES
twitter 2