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Small Molecules to Improve ER Proteostasis in Disease.
- Source :
-
Trends in pharmacological sciences [Trends Pharmacol Sci] 2019 Sep; Vol. 40 (9), pp. 684-695. Date of Electronic Publication: 2019 Jul 31. - Publication Year :
- 2019
-
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.<br /> (Copyright © 2019. Published by Elsevier Ltd.)
- Subjects :
- Animals
Endoplasmic Reticulum metabolism
Humans
Metabolic Diseases metabolism
Neoplasms metabolism
Neurodegenerative Diseases metabolism
Proteostasis drug effects
Unfolded Protein Response drug effects
Endoplasmic Reticulum drug effects
Metabolic Diseases drug therapy
Neoplasms drug therapy
Neurodegenerative Diseases drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1873-3735
- Volume :
- 40
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Trends in pharmacological sciences
- Publication Type :
- Academic Journal
- Accession number :
- 31377018
- Full Text :
- https://doi.org/10.1016/j.tips.2019.07.003