The unfolded protein response in Alzheimer's disease

Semin Immunopathol. 2013 May;35(3):277-92. doi: 10.1007/s00281-013-0373-9. Epub 2013 Apr 23.


Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by synaptic dysfunction and accumulation of amyloid-beta (Aβ) peptide, which are responsible for the progressive loss of memory. The mechanisms involved in neuron dysfunction in AD remain poorly understood. Recent evidence implicates the participation of adaptive responses to stress within the endoplasmic reticulum (ER) in the disease process, via a pathway known as the unfolded protein response (UPR). Here, we review the findings suggesting a functional role of ER stress in the etiology of AD. Possible therapeutic strategies to mitigate ER stress in the context of AD are discussed.

Publication types

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

MeSH terms

  • Alzheimer Disease / etiology*
  • Amyloid beta-Protein Precursor / metabolism
  • Animals
  • Endoplasmic Reticulum Stress
  • Humans
  • Neurons / metabolism
  • Presenilins / metabolism
  • Proteolysis
  • Signal Transduction
  • Tauopathies / metabolism
  • Tauopathies / physiopathology
  • Unfolded Protein Response*


  • Amyloid beta-Protein Precursor
  • Presenilins