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Neuroglia: Functional Paralysis and Reactivity in Alzheimer’s Disease and Other Neurodegenerative Pathologies

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Neurodegenerative Diseases

Part of the book series: Advances in Neurobiology ((NEUROBIOL,volume 15))

Abstract

The most notable finding in neurodegenerative diseases is the progressive death of neurones cells. Yet, neuroglial changes can precede and facilitate neuronal loss. This is perhaps expected because astroglial cells maintain the brain homoeostasis, and are responsible for defence and regeneration, so that their malfunction manifested as degeneration or asthenia together with reactivity contribute to pathophysiology. Neuroglia may represent a novel target for therapeutic intervention, be that prevention, slowing progression of or possibly curing neurodegenerative diseases.

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Abbreviations

3xTg-AD:

Triple transgenic mouse model of Alzheimer’s disease, overexpressing mutant genes for amyloid precursor protein (APPSwe), presenilin 1 (PS1M146V) and microtubule-associated protein Tau (TauP301L)

AD:

Alzheimer’s disease

ALS:

Amyotrophic lateral sclerosis

APP:

Amyloid precursor protein

CNS:

Central nervous system

CPA:

Cyclopiazonic acid

DAT1:

Dopamine transporter1

EAAT2:

Excitable amino acid transporter 2

ER:

Endoplasmic reticulum

HD:

Huntington disease

GRP78:

78 kDa glucose-regulated protein

IDE:

Insulin degrading enzyme InsP3: inositol 1,4,5-trisphosphate

JAK/STAT3:

Janus kinase/signal transducers and activators of transcription

L-DOPA:

L-3,4-Dihydroxyphenylalanine

MHC-II:

Major histocompatibility complex II

mRNA:

Messenger RNA

NFAT:

Nuclear factor of activated T-cells

PD:

Parkinson disease

NF-κB:

Nuclear factor kappa-light-chain-enhancer of activated B cells

PS1:

Presenilin 1

SOCE:

Store-operated Ca2+ entry

SOD1:

Superoxide dismutase 1

TLR2, TLR4:

Toll receptors 2, 4

UPR:

Unfolded protein response

VGLUT1:

Vesicular l-glutamate transporter

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Acknowledgements

Authors research was supported by Alzheimer’s Research Trust (UK) Programme Grant (ART/PG2004A/1) to A.V. and J.J.R.; by National Institutes of Health (The Eunice Kennedy Shriver National Institute of Child Health and Human Development award HD078678) to V.P.; by the grants P3 310, J3 4051, J3 3632, J3 6790, J3 7605 and J3 4146 from the Slovenian Research Agency (ARRS) and the EduGlia ITN EU grant to R.Z. and A.V.; by Plan Nacional de I+D+I 2008–2011 and ISCIII-Subdirección General de Evaluación y Fomento de la investigación co-financed by FEDER (grant PI10/02738 to J.J.R. and A.V.); by the Government of the Basque Country grants AE-2010-1-28, AEGV10/16 and GV-2011111020 to J.J.R. A.V. was also supported by the Federal Target Program “Research and development in priority areas of the development of the scientific and technological complex of Russia for 2014–2020” of the Ministry of Education and Science of Russia, contract 14.581.21.0016 (Project ID RFMEFI58115X0016).

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Authors and Affiliations

  1. Faculty of Life Sciences, The University of Manchester, Oxford Road, Manchester, M13 9PT, UK

    Alexei Verkhratsky M.D., Ph.D.

  2. Achucarro Center for Neuroscience, IKERBASQUE, Basque Foundation for Science, 48011, Bilbao, Spain

    Alexei Verkhratsky M.D., Ph.D. & J. J. Rodriguez Ph.D.

  3. Department of Neurosciences, University of the Basque Country UPV/EHU and CIBERNED, Leioa, Spain

    Alexei Verkhratsky M.D., Ph.D. & J. J. Rodriguez Ph.D.

  4. University of Nizhny Novgorod, Nizhny Novgorod, 603022, Russia

    Alexei Verkhratsky M.D., Ph.D.

  5. Laboratory of Neuroendocrinology and Molecular Cell Physiology, Institute of Pathophysiology, University of Ljubljana, Zaloska cesta 4, 1000, Ljubljana, Slovenia

    Alexei Verkhratsky M.D., Ph.D. & Robert Zorec

  6. Celica, BIOMEDICAL, Technology Park 24, 1000, Ljubljana, Slovenia

    Robert Zorec

  7. Department of Neurobiology, Civitan International Research Center and Center for Glial Biology in Medicine, Evelyn F. McKnight Brain Institute, Atomic Force Microscopy & Nanotechnology Laboratories, University of Alabama, 1719 6th Avenue South, CIRC 429, Birmingham, AL, 35294-0021, USA

    Vladimir Parpura M.D., Ph.D.

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  1. Alexei Verkhratsky M.D., Ph.D.
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  2. Robert Zorec
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  3. J. J. Rodriguez Ph.D.
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  4. Vladimir Parpura M.D., Ph.D.
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Correspondence to Alexei Verkhratsky M.D., Ph.D. .

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  1. University of Melbourne Florey Institute of Neuroscience and Mental Health, Parkville, Australia

    Philip Beart

  2. Pediatrics and Pharmacology Children’s Hospital of Philadelphia, University of Pennsylvania, Philadelphia, Pennsylvania, USA

    Michael Robinson

  3. School of Life Sciences Bradford School of Pharmacy, University of Bradford, Bradford, United Kingdom

    Marcus Rattray

  4. Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA

    Nicholas J. Maragakis

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Verkhratsky, A., Zorec, R., Rodriguez, J.J., Parpura, V. (2017). Neuroglia: Functional Paralysis and Reactivity in Alzheimer’s Disease and Other Neurodegenerative Pathologies. In: Beart, P., Robinson, M., Rattray, M., Maragakis, N. (eds) Neurodegenerative Diseases. Advances in Neurobiology, vol 15. Springer, Cham. https://doi.org/10.1007/978-3-319-57193-5_17

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