The role of endoplasmic reticulum in amyloid precursor protein processing and trafficking: implications for Alzheimer's disease

AI Plácido, CMF Pereira, AI Duarte, E Candeias, SC Correia, RX Santos, C Carvalho, S Cardoso, CR Oliveira, PI Moreira*

*Corresponding author for this work

Research output: Contribution to journalArticle

63 Citations (Scopus)

Abstract

The endoplasmic reticulum (ER) is the principal organelle responsible for the proper folding/processing of nascent proteins and perturbed ER function leads to a state known as ER stress. Mammalian cells try to overcome ER stress through a set of protein signaling pathways and transcription factors termed the unfolded protein response (UPR). However, under unresolvable ER stress conditions, the UPR is hyperactivated inducing cell dysfunction and death. The accumulation of misfolded proteins in the brain of Alzheimer's disease (AD) patients suggests that alterations in ER homeostasis might be implicated in the neurodegenerative events that characterize this disorder. This review discusses the involvement of ER stress in the pathogenesis of AD, focusing the processing and trafficking of the AD-related amyloid precursor protein (APP) during disease development. The potential role of ER as a therapeutic target in AD will also be debated.
Original languageEnglish
Pages (from-to)1444-1453
Number of pages10
JournalBiochimica et Biophysica Acta
Volume1842
Issue number9
Early online date14 May 2014
DOIs
Publication statusPublished - Sep 2014

Keywords

  • Alzheimer's disease
  • amyloid precursor protein
  • endoplasmic reticulum
  • secretory pathway
  • therapeutic targets
  • trafficking

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    Plácido, AI., Pereira, CMF., Duarte, AI., Candeias, E., Correia, SC., Santos, RX., Carvalho, C., Cardoso, S., Oliveira, CR., & Moreira, PI. (2014). The role of endoplasmic reticulum in amyloid precursor protein processing and trafficking: implications for Alzheimer's disease. Biochimica et Biophysica Acta, 1842(9), 1444-1453. https://doi.org/10.1016/j.bbadis.2014.05.003