Small Molecules to Improve ER Proteostasis in Disease

Trends in Pharmacological Sciences
Vicente Gonzalez-TeuberClaudio Hetz

Abstract

Abnormally high levels of misfolded proteins in the endoplasmic reticulum (ER) lumen result in a stress state that contributes to the progression of several pathological conditions including diabetes, cancer, neurodegeneration, and immune dysregulation. ER stress triggers a dynamic signaling pathway known as the unfolded protein response (UPR). The UPR enforces adaptive or cell death programs by integrating information about the intensity and duration of the stress stimuli. Thus, depending on the disease context, ER stress signaling can be beneficial or detrimental. We discuss current efforts to develop small molecules to target distinct components of the UPR, and their possible applications in treating human disease, focusing on neurodegenerative diseases, metabolic disorders, and cancer.

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Citations

Nov 14, 2019·International Journal of Molecular Sciences·Yurong GaoJaemin Lee
Jun 12, 2020·Antioxidants & Redox Signaling·Hugo PothionIsabelle Lihrmann
Feb 11, 2020·Frontiers in Cell and Developmental Biology·Carsten J BeeseLisa B Frankel
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Apr 4, 2021·Biomolecules·Meytal RadzinskiDana Reichmann
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Jul 2, 2020·ACS Chemical Biology·Dale TranterVille O Paavilainen
Oct 16, 2021·ACS Chemical Neuroscience·A Katherine HatstatDewey G McCafferty

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