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Pharmacological targeting of endoplasmic reticulum stress in disease.

Accepted version
Peer-reviewed

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Type

Article

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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.

Description

Keywords

Animals, Endoplasmic Reticulum Stress, Humans, Metabolic Diseases, Neoplasms, Nervous System Diseases, Unfolded Protein Response

Journal Title

Nat Rev Drug Discov

Conference Name

Journal ISSN

1474-1776
1474-1784

Volume Title

Publisher

Springer Science and Business Media LLC
Sponsorship
Wellcome Trust (100140/Z/12/Z)
Wellcome Trust (200848/Z/16/Z)
Medical Research Council (MR/R009120/1)
MRC (MR/V028669/1)
National Institute for Health and Care Research (IS-BRC-1215-20014)
Medical Research Council (G1002610)
Engineering and Physical Sciences Research Council (EP/S009000/1)