Unfolded proteins and endoplasmic reticulum stress in neurodegenerative disorders

J Cell Mol Med. 2011 Oct;15(10):2025-39. doi: 10.1111/j.1582-4934.2011.01374.x.

Abstract

The stimuli for neuronal cell death in neurodegenerative disorders are multi-factorial and may include genetic predisposition, environmental factors, cellular stressors such as oxidative stress and free radical production, bioenergy failure, glutamate-induced excitotoxicity, neuroinflammation, disruption of Ca(2+) -regulating systems, mitochondrial dysfunction and misfolded protein accumulation. Cellular stress disrupts functioning of the endoplasmic reticulum (ER), a critical organelle for protein quality control, leading to induction of the unfolded protein response (UPR). ER stress may contribute to neurodegeneration in a range of neurodegenerative disorders. This review summarizes the molecular events occurring during ER stress and the unfolded protein response and it specifically evaluates the evidence suggesting the ER stress response plays a role in neurodegenerative disorders.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Activating Transcription Factor 6 / genetics
  • Activating Transcription Factor 6 / metabolism
  • Alzheimer Disease / genetics
  • Alzheimer Disease / metabolism
  • Amyotrophic Lateral Sclerosis / genetics
  • Amyotrophic Lateral Sclerosis / metabolism
  • Apoptosis
  • Autophagy / genetics
  • Endoplasmic Reticulum Stress*
  • Endoribonucleases / genetics
  • Endoribonucleases / metabolism
  • Humans
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Neurodegenerative Diseases / genetics
  • Neurodegenerative Diseases / metabolism*
  • Parkinson Disease / genetics
  • Parkinson Disease / metabolism
  • Prion Diseases / genetics
  • Prion Diseases / metabolism
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism
  • Unfolded Protein Response*
  • eIF-2 Kinase / genetics
  • eIF-2 Kinase / metabolism

Substances

  • ATF6 protein, human
  • Activating Transcription Factor 6
  • Membrane Proteins
  • ERN2 protein, human
  • PERK kinase
  • Protein Serine-Threonine Kinases
  • eIF-2 Kinase
  • Endoribonucleases