Endoplasmic reticulum stress in diseases
Open Access
Abstract
The endoplasmic reticulum (ER) is a key organelle in eukaryotic cells, responsible for a wide range of vital functions, including the modification, folding, and trafficking of proteins, as well as the biosynthesis of lipids and the maintenance of intracellular calcium homeostasis. A variety of factors can disrupt the function of the ER, leading to the aggregation of unfolded and misfolded proteins within its confines and the induction of ER stress. A conserved cascade of signaling events known as the unfolded protein response (UPR) has evolved to relieve the burden within the ER and restore ER homeostasis. However, these processes can culminate in cell death while ER stress is sustained over an extended period and at elevated levels. This review summarizes the potential role of ER stress and the UPR in determining cell fate and function in various diseases, including cardiovascular diseases, neurodegenerative diseases, metabolic diseases, autoimmune diseases, fibrotic diseases, viral infections, and cancer. It also puts forward that the manipulation of this intricate signaling pathway may represent a novel target for drug discovery and innovative therapeutic strategies in the context of human diseases.Keywords
This publication has 290 references indexed in Scilit:
- Calpain and calpastatin regulate neutrophil apoptosisJournal of Cellular Physiology, 1999
- Protein translation and folding are coupled by an endoplasmic-reticulum-resident kinaseNature, 1999
- Protein Disulfide Isomerase Assists Protein Folding as Both an Isomerase and a ChaperoneaAnnals of the New York Academy of Sciences, 1998
- The Chaperone BiP/GRP78 Binds to Amyloid Precursor Protein and Decreases Aβ40 and Aβ42 SecretionJournal of Biological Chemistry, 1998
- The Mechanism of Ca2+ Transport by Sarco(Endo)plasmic Reticulum Ca2+-ATPasesJournal of Biological Chemistry, 1997
- A novel signal transduction pathway from the endoplasmic reticulum to the nucleus is mediated by transcription factor NF‐kappa B.The EMBO Journal, 1995
- Alzheimer's Disease: The Amyloid Cascade HypothesisScience, 1992
- Generation of Calcium Oscillations in Fibroblasts by Positive Feedback Between Calcium and IP 3Science, 1991
- Microtubule-associated protein tau (tau) is a major antigenic component of paired helical filaments in Alzheimer disease.Proceedings of the National Academy of Sciences, 1986
- Wolcott-Rallison syndrome: Diabetes mellitus and spondyloepiphyseal dysplasiaEuropean Journal of Pediatrics, 1982