Pharmacological targeting of endoplasmic reticulum stress in disease.
Nat Rev Drug Discov
Springer Science and Business Media LLC
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Marciniak, S. J., Chambers, J. E., & Ron, D. (2022). Pharmacological targeting of endoplasmic reticulum stress in disease.. Nat Rev Drug Discov https://doi.org/10.1038/s41573-021-00320-3
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.
Wellcome Trust (100140/Z/12/Z)
Wellcome Trust (200848/Z/16/Z)
Medical Research Council (MR/R009120/1)
National Institute for Health Research (IS-BRC-1215-20014)
Medical Research Council (G1002610)
Engineering and Physical Sciences Research Council (EP/S009000/1)
External DOI: https://doi.org/10.1038/s41573-021-00320-3
This record's URL: https://www.repository.cam.ac.uk/handle/1810/330477
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