Endoplasmic Reticulum Stress: Implications in Diseases

Abstract

Endoplasmic reticulum (ER) is a specialized organelle that plays a significant role in cellular function. The major functions of ER include protein synthesis and transport, folding of proteins, biosynthesis of lipids, calcium (Ca²⁺) storage, and redox balance. The loss of ER integrity results in the induction of ER stress within the cell due to the accumulation of unfolded, improperly folded proteins or changes in Ca²⁺ metabolism and redox balance of organelle. This ER stress commences the Unfolded Protein Response (UPR) that serves to counteract the ER stress via three sensors inositol requiring protein–1 (IRE1), protein kinase RNA-like ER kinase (PERK), and activating transcription factor–6 (ATF6) that serve to establish ER homeostasis and alleviates ER stress. Severe ER dysfunction ultimately results in the induction of apoptosis. Increasing shreds of evidence suggest the implication of ER stress in the development and progression of several diseases viz. tuberculosis, malaria, Alzheimer’s disease, Parkinson’s disease, diabetes, and cancer. Activation of ER stress can be beneficial for treating some diseases while inhibiting the process can be useful in others. A deeper understanding of these pathways can provide key insights in designing novel therapeutics to treat these diseases.