Alzheimer's disease pathology and the unfolded protein response

Prospective pathways and therapeutic targets

David J Koss*, Bettina Platt

*Corresponding author for this work

Research output: Contribution to journalReview article

4 Citations (Scopus)
9 Downloads (Pure)

Abstract

Many vital interdependent cellular functions including proteostasis, lipogenesis and Ca2+ homeostasis are executed by the endoplasmic reticulum (ER). Exogenous insults can impair ER performance: this must be rapidly corrected or cell death will ensue. Protective adaptations can boost the functional capacity of the ER and form the basis of the unfolded protein response (UPR). Activated in response to the accumulation of misfolded proteins, the UPR can halt protein translation while increasing protein-handling chaperones and the degradation of erroneous proteins through a conserved three-tier molecular cascade. However, prolonged activation of the UPR can result in the maladaptation of the system, resulting in the activation of inflammatory and apoptotic effectors. Recently, UPR and its involvement in neurodegenerative disease has attracted much interest and numerous potentially 'drugable' points of crosstalk are now emerging. Here, we summarize the functions of the ER and UPR, and highlight evidence for its potential role in the pathogenesis of Alzheimer's disease, before discussing several key targets with therapeutic potential.
Original languageEnglish
Pages (from-to)161-178
Number of pages18
JournalBehavioural Pharmacology
Volume28
Issue number2 and 3 - Special Issue
Early online date2 Mar 2017
DOIs
Publication statusPublished - 1 Apr 2017

Fingerprint

Unfolded Protein Response
Alzheimer Disease
Endoplasmic Reticulum
Pathology
Therapeutics
Protein Unfolding
Lipogenesis
Protein Biosynthesis
Neurodegenerative Diseases
Proteolysis
Homeostasis
Cell Death
Proteins

Keywords

  • amyloid
  • Alzheimers Disease
  • apoptosis
  • endoplasmic reticulum
  • endoplasmic reticulum stress
  • tau
  • neurodegeneration
  • homeostasis
  • proteostasis
  • drug discovery

Cite this

Alzheimer's disease pathology and the unfolded protein response : Prospective pathways and therapeutic targets. / Koss, David J; Platt, Bettina.

In: Behavioural Pharmacology, Vol. 28, No. 2 and 3 - Special Issue, 01.04.2017, p. 161-178.

Research output: Contribution to journalReview article

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