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Role of ER Stress in Dysfunction of the Nervous System

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Endoplasmic Reticulum Stress in Health and Disease

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Abstract

Recent clinical, genetic and experimental evidence indicates that dysregulation of endoplasmic reticulum (ER) homeostasis plays an important role in the pathogenesis of neurodegenerative diseases and psychiatric illness. Protein flux through the ER must be carefully monitored to prevent dysregulation of ER homeostasis and stress. ER stress elicits a signaling cascade known as the unfolded protein response (UPR) which functions in influencing both cellular life and death decisions. In this chapter, we address the transition from the physiological ER stress response to the pathological response and explore the mechanisms of ER stress-mediated dysfunction and death of neurons during the progression of neurodegenerative diseases and psychiatric illness.

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Abbreviations

ER:

Endoplasmic reticulum

UPR:

Unfolded protein response

PERK:

PKR-like ER kinase

CHOP:

C/EBP Thomologous protein

eIF2a:

Eukaryotic initiation factor 2a

PD:

Parkinson’s disease

AJ-PD:

Autosomal recessive juvenile-onset Parkinson’s disease

Pael-R:

Pael-receptor

SPG:

Spastic paraplegia

BSCL2:

Berardinelli-Seip congenital lipodystrophy 2

ALS:

Amyotrophic lateral sclerosis

SOD1:

Superoxide dismutase 1

PDI:

Protein disulfide isomerase

PUMA:

P53-upregulated mediator of apoptosis

RP:

Retinitis pigmentosa

ERAD:

ER associated degradation

AD:

Alzheimer’s disease

PS:

Presenilin

IRE1:

Inositol-requiring enzyme 1

NMDA:

N-methy D-aspartate

NOS:

nitric oxide synthase

XBP1:

X-box binding protein 1

CHOP:

CCAAT/enhancer binding protein homologous protein

MSS:

Marinesco-Sjogren syndrome

IBMPFD:

Inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia

αSyn:

α-synuclein

SERCA:

Sarco-endoplasmic reticulum Ca2 + ATPase pump

IP3 receptor:

Inositol triphosphate-gated channel

SCA:

Spinocerebeller atrophy

OASIS:

Old astrocyte specifically-induced substrate

ATF6:

Activating transcription factor 6

CLN1:

Neuronal ceroid lipofuscinosis 1

PPT1:

Palmitoyl protein thioesterase 1

TMAO:

Trimethylamine N-oxide

TUDCA:

Tauroursodeoxycholic acid

PMD:

Pelizaeus Merzbacher disease

PLP1:

Proteolipid protein-1

P0:

Myelin protein zero

VWMD:

Vanishing White Matter Disease

GEF:

Guanine nucleotide exchanging factor

ASD:

Autism spectrum disorder

CADM1:

Cell adhesion molecule-1

DIDMOAD:

Diabetes Insipidus, Diabetes Mellitus, Optic Atrophy and Deafness

WFS1:

Wolfram syndrome 1

CISD2:

CDGSH iron sulfur domain 2

MRI:

Magnetic resonance imaging

4PBA:

4-phenylbutylate

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Acknowledgements

Work in the laboratory of F. Urano is supported by grants from NIH-NIDDK (R01DK067493), the Diabetes and Endocrinology Research Center at the University of Massachusetts Medical School (5 P30 DK32520), and the Juvenile Diabetes Research Foundation International (1-2008-593 and 40-2011-14). K.K. is supported by Japan Society for the Promotion of Science.

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Authors and Affiliations

  1. Program in Molecular Medicine, University of Massachusetts Medical School, 01605, Worcester, MA, USA

    Kohsuke Kanekura, Simin Lu & Fumihiko Urano

  2. Program in Gene Function and Expression, University of Massachusetts Medical School, 364 Plantation Street, Room 522, 01605, Worcester, MA, USA

    Fumihiko Urano

  3. Department of Physical and Biological Sciences, Western New England University, 01119, Springfield, MA, USA

    Kathryn L. Lipson

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  1. Kohsuke Kanekura
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  2. Simin Lu
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  3. Kathryn L. Lipson
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  4. Fumihiko Urano
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Correspondence to Fumihiko Urano .

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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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Kanekura, K., Lu, S., Lipson, K., Urano, F. (2012). Role of ER Stress in Dysfunction of the Nervous System. 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_13

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