Endoplasmic reticulum stress in diseases

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. The endoplasmic reticulum (ER) serves as a vital organelle in eukaryotic cells, performing essential roles such as protein folding, modification, and trafficking, lipid biosynthesis, and calcium regulation. Various conditions may disrupt ER function, potentially leading to the accumulation of unfolded and misfolded proteins, and triggering ER stress. This prompts the unfolded protein response (UPR), a conserved signaling cascade, to mitigate the stress by regulating gene expression and protein synthesis, aiming to restore ER equilibrium. However, prolonged or severe ER stress can lead to cell death. As our understanding of the molecular mechanisms linking ER stress to human diseases improves, ER stress and UPR activation are increasingly recognized as significant contributors to various diseases. The balancing of ER stress and the UPR is crucial for the pathogenesis of diseases, such as cardiovascular diseases, neurodegenerative diseases, metabolic diseases, autoimmune diseases, fibrotic diseases, viral infections, and cancer. It also considers how manipulation of this complex signaling pathway may provide a new target for drug discovery and innovative therapeutic strategies in human disease. image