'Unfolding' pathways in neurodegenerative disease

Trends Neurosci. 2003 Aug;26(8):407-10. doi: 10.1016/S0166-2236(03)00197-8.


The endoplasmic reticulum responds to stress by initiating a cascade of events known as the 'unfolded-protein response' (UPR). The accumulation of misfolded proteins in the leukodystrophy Pelizaeus-Merzbacher disease activates this stress response, resulting in apoptosis of oligodendrocytes. Although it remains uncertain whether the UPR plays a mechanistic role in prototypical neurodegenerative disorders such as Alzheimer's disease, this is plausible because misfolded proteins are directly implicated in the pathogenesis of these disorders.

Publication types

  • Review

MeSH terms

  • Adaptation, Physiological
  • Alzheimer Disease / physiopathology
  • Animals
  • Apoptosis
  • Endoplasmic Reticulum / chemistry*
  • Endoplasmic Reticulum / metabolism*
  • Humans
  • Membrane Proteins / physiology
  • Mice
  • Neurodegenerative Diseases / physiopathology*
  • Parkinson Disease / physiopathology
  • Pelizaeus-Merzbacher Disease / physiopathology
  • Protein Conformation*
  • Protein Folding*
  • Stress, Physiological / physiopathology*


  • Membrane Proteins