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The endoplasmic reticulum unfolded protein response and neurodegeneration

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Protein Quality Control in Neurodegenerative Diseases

Part of the book series: Research and Perspectives in Alzheimer's Disease ((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.

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  1. University of Cambridge Metabolic Research Laboratories and NIHR Cambridge Biomedical Research Centre, MRL, level 4, Addenbrooke’s Hospital, 289, Hills Road, Cambridge, CB2 0QQ, UK

    David Ron

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  1. Morimoto Lab, Northwestern University, 2205 Tech Drive, Evanston, 60208-3500, Illinois, USA

    Richard I. Morimoto

  2. Fondation IPSEN, Quai Georges Gorse 65, Boulogne-Billancourt Cedex, 92650, France

    Yves Christen

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Ron, D. (2013). The endoplasmic reticulum unfolded protein response and neurodegeneration. In: Morimoto, R., Christen, Y. (eds) Protein Quality Control in Neurodegenerative Diseases. Research and Perspectives in Alzheimer's Disease. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-27928-7_2

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