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The endoplasmic reticulum unfolded protein response and neurodegeneration

  • David Ron
Chapter
Part of the Research and Perspectives in Alzheimer's Disease book series (ALZHEIMER)

Abstract

Proteostasis in the lumen of the endoplasmic reticulum is defended by signalling pathways that match the load of unfolded proteins to the complement of chaperones in the organelle. This balancing act is attained via a transcriptional program that activates genes encoding chaperones and other proteins that function in the secretory pathway and a translational program that transiently attenuates protein synthesis by regulating translation initiation. The key features of this unfolded protein response (UPR) will be reviewed, with an emphasis on those strands that are known to intersect with neurophysiology and neuropathology. A particular focus for review will be the evidence that activity of the translational arm of the UPR impacts on diverse phenomena ranging from memory consolidation to myelination and that the transcriptional arm of the UPR is in equilibrium with other pathways that defend proteostasis. Specific consideration will be given to points for intervention in the working of the UPR and how these might be harnessed for treatment of neurological disease.

Keywords

Endoplasmic Reticulum Endoplasmic Reticulum Stress Unfold Protein Response Gene Expression Program Unfold Protein Response Activity 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  1. 1.University of Cambridge Metabolic Research Laboratories and NIHR Cambridge Biomedical Research Centre, MRL, level 4, Addenbrooke’s HospitalCambridgeUK

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