Targeting unfolded protein response: a new horizon for disease control

Expert Rev Mol Med. 2021 Mar 4:23:e1. doi: 10.1017/erm.2021.2.

Abstract

Unfolded protein response (UPR) is an evolutionarily conserved pathway triggered during perturbation of endoplasmic reticulum (ER) homeostasis in response to the accumulation of unfolded/misfolded proteins under various stress conditions like viral infection, diseased states etc. It is an adaptive signalling cascade with the main purpose of relieving the stress from the ER, which may otherwise lead to the initiation of cell death via apoptosis. ER stress if prolonged, contribute to the aetiology of various diseases like cancer, type II diabetes, neurodegenerative diseases, viral infections etc. Understanding the role of UPR in disease progression will help design pharmacological drugs targeting the sensors of signalling cascade acting as potential therapeutic agents against various diseases. The current review aims at highlighting the relevance of different pathways of UPR in disease progression and control, including the available pharmaceutical interventions responsible for ameliorating diseased state via modulating UPR pathways.

Keywords: Cancer; ER stress; neurodegenerative diseases; therapeutic intervention; type II diabetes; unfolded protein response pathways; viral infection.

Publication types

  • Review

MeSH terms

  • Diabetes Mellitus, Type 2* / metabolism
  • Endoplasmic Reticulum / metabolism
  • Endoplasmic Reticulum Stress
  • Humans
  • Signal Transduction
  • Unfolded Protein Response