The unfolded protein response is involved in the pathology of Alzheimer's disease

Ann N Y Acad Sci. 2002 Nov;977:349-55. doi: 10.1111/j.1749-6632.2002.tb04837.x.

Abstract

The endoplasmic reticulum (ER) performs the synthesis, posttranslational modification, and proper folding of proteins. A variety of conditions can be ER stress, causing the accumulation of unfolding or misfolding proteins in the ER. Eukaryotic cells have three different mechanisms for dealing with an accumulation of unfolded proteins in the ER known as the unfolded protein response (UPR): transcriptional induction, translational attenuation, and degradation. This paper focuses on the relationship between UPR and the pathogenesis of AD. Our results indicate a new mechanism by which PS1 mutations may affect the sensing of ER stress. Experimental manipulation of IRE1, PERK, or eIF2alpha phosphorylation or GRP78 expression might allow the development of therapeutic strategies for FAD.

MeSH terms

  • Alzheimer Disease / genetics
  • Alzheimer Disease / pathology*
  • Autoantigens / genetics
  • Carrier Proteins / genetics
  • Endoplasmic Reticulum / pathology
  • Heat-Shock Proteins*
  • Humans
  • Membrane Proteins / chemistry
  • Membrane Proteins / metabolism
  • Models, Neurological
  • Molecular Chaperones / genetics
  • Protein Conformation
  • Protein Denaturation*
  • RNA, Messenger / genetics

Substances

  • Autoantigens
  • Carrier Proteins
  • Heat-Shock Proteins
  • Membrane Proteins
  • Molecular Chaperones
  • RNA, Messenger
  • molecular chaperone GRP78