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Current advances in ER stress intervention therapies

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Endoplasmic Reticulum Stress in Health and Disease

Abstract

The endoplasmic reticulum (ER) is the site of synthesis and folding of membrane-localised and secretory proteins. The load upon ER client proteins that cells process varies considerably depending on cell type and physiological state and cells adapt to this variation by modulating both the capacity of the ER to process proteins and the load of client proteins synthesised. The flux of proteins through the ER is carefully monitored by cells for abnormalities, including a build up of mis-folded proteins. Mammalian cells have evolved an intricate set of signalling pathways from the ER to the cytosol and nucleus, to allow the cell to respond to the presence of misfolded proteins within the ER. These pathways, known collectively as the unfolded protein response (UPR), are important for normal cellular homeostasis and organism development and may play key roles in the pathogenesis of many diseases. In this chapter we will discuss a number of diseases whose pathogenesis involves ER stress and UPR. In addition we discuss the potential therapeutic avenues available for modulation of ER stress in disease states and autophagy.

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Abbreviations

PERK:

PRK-like endoplasmic reticulum kinase

UPR:

unfolded protein response

ER:

endoplasmic reticulum

PI3 K:

phosphatidyl inositol 3 kinase

MAPK:

mitogen activated protein kinase

JNK:

c-Jun NH2-terminal kinase

PTEN:

phosphatase and tensin homologue on chromosome ten

ROS:

reactive oxygen species

PP:

protein phosphatase

HIF:

Hypoxia Inducible Factor

GRP:

glucose regulated protein

ATF:

activating transcription factor

XBP:

X-box binding protein

CHOP:

CCAAT/-enhancer-binding protein homologous protein

SERCA:

Sarco/Endoplasmic Reticulum Ca2 + -ATPase

IRE1:

Inositol-requiring protein 2, Serine/threonine-protein kinase/endoribonuclease

ERAD:

ER-associated protein degradation

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Authors and Affiliations

  1. Departments of Neurosurgery, Virginia Commonwealth University, 401 College St, 23298, Richmond, VA, USA

    Laurence A. Booth, Nichola Cruickshanks, Yong Tang, M. Danielle Bareford, Hossein A. Hamed & Paul Dent

  2. Human and Molecular Genetics, Virginia Commonwealth University, 401 College St, 23298, Richmond, VA, USA

    Paul B. Fisher

  3. Medicine, Virginia Commonwealth University, 401 College St, 23298, Richmond, VA, USA

    Steven Grant

  4. Virginia Institute of Molecular Medicine, Virginia Commonwealth University, 401 College St, 23298, Richmond, VA, USA

    Paul B. Fisher, Steven Grant & Paul Dent

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  1. Laurence A. Booth
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  8. Paul Dent
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  1. Dept Molec Cell Bio, K.U. Leuven, Harestraat/Gasthuisberg, B-3000 Leuven, 3000, Belgium

    Patrizia Agostinis

  2. School of Natural Science, Department of Biochemistry, NUI Galway, University Road, Galway, Ireland

    Samali Afshin

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© 2012 Springer Science+Business Media Dordrecht

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Booth, L. et al. (2012). Current advances in ER stress intervention therapies. In: Agostinis, P., Afshin, S. (eds) Endoplasmic Reticulum Stress in Health and Disease. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-4351-9_19

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