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Role of Endoplasmic Reticulum in Non-communicable Diseases

Tesfamariam Alias, Natesan Gnanasekaran

Abstract


Endoplasmic reticulum (ER) is a large membrane-bound organelle that provides high fidelity quality control in protein synthesis, maturation and transport. There are two distinct types of ER that differ in structure and function: smooth ER and rough ER. The complex function of the ER can be significantly influenced by various factors both inside the cell and in its microenvironment. Disturbances in ER protein folding capacity result in accumulation of misfolded proteins in the ER lumen and in activation of ER stress. The unfolded protein response normally has pro-survival functions and protects cells by providing the reestablishment of protein processing and cellular homeostasis. However, prolonged and excessive ER stress results in activation of apoptotic pathways. Therefore, the persistent protein misfolding initiates apoptotic cascades that are now known to play fundamental roles in the pathogenesis of multiple human diseases including diabetes, atherosclerosis and neurodegenerative diseases. With the improved understanding of the underlying molecular mechanisms, therapeutic interventions that target the ER stress response would be potential strategies to treat various diseases driven by prolonged ER stress.

Keywords


ER stress, unfolded protein response (UPR), neurodegenerative disease, liver disease, atherosclerosis, diabetes, cancer

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