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Astrocytes: a central element in neurological diseases

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Abstract

The neurone-centred view of the past disregarded or downplayed the role of astroglia as a primary component in the pathogenesis of neurological diseases. As this concept is changing, so is also the perceived role of astrocytes in the healthy and diseased brain and spinal cord. We have started to unravel the different signalling mechanisms that trigger specific molecular, morphological and functional changes in reactive astrocytes that are critical for repairing tissue and maintaining function in CNS pathologies, such as neurotrauma, stroke, or neurodegenerative diseases. An increasing body of evidence shows that the effects of astrogliosis on the neural tissue and its functions are not uniform or stereotypic, but vary in a context-specific manner from astrogliosis being an adaptive beneficial response under some circumstances to a maladaptive and deleterious process in another context. There is a growing support for the concept of astrocytopathies in which the disruption of normal astrocyte functions, astrodegeneration or dysfunctional/maladaptive astrogliosis are the primary cause or the main factor in neurological dysfunction and disease. This review describes the multiple roles of astrocytes in the healthy CNS, discusses the diversity of astroglial responses in neurological disorders and argues that targeting astrocytes may represent an effective therapeutic strategy for Alexander disease, neurotrauma, stroke, epilepsy and Alzheimer’s disease as well as other neurodegenerative diseases.

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Acknowledgments

The authors thank Roy Pekny for critical comments on the manuscript and acknowledge support from the Swedish Medical Research Council (Project 11548 and 20116), Deutsche Forschungsgemeinschaft (STE 552/3), AFA Research Foundation, ALF Göteborg (Project 11392 and 142821), Sten A. Olsson Foundation for Research and Culture, Söderberg Foundations, Hjärnfonden, Hagströmer’s Foundation Millennium, the Swedish Stroke Foundation, the Swedish Society for Medical Research, the Free Mason Foundation, Amlöv’s Foundation, E. Jacobson’s Donation Fund, NanoNet COST Action, (BM1002), the EU FP 7 Programs EduGlia (237956), NeuroGLIA (202167), EuroEPINOMICS and TargetBraIn (279017). AV was supported, in part, by the Grant (agreement from August 27 2013 No. 02.B.49.21.0003) between The Ministry of Education and Science of the Russian Federation and Lobachevsky State University of Nizhny Novgorod, by the Ministry of education of Russian Federation, unique identity number of the project is RFMEFI57814X0079, and by the grant of the Russian Scientific Foundation No. 14-15-00633. VP’s work is supported by the National Institutes of Health (HD078678). The concept of this review was conceived at the conference and training school Astrocyte Intermediate Filaments (Nanofilaments) and Astrocyte Function in Health and Disease, held at the University of Gothenburg, Sweden, in 2014, supported by NanoNet COST Action (BM1002), and the Swedish Medical Research Council, with the authors of this review as speakers.

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Authors and Affiliations

  1. Department of Clinical Neuroscience and Rehabilitation, Center for Brain Repair and Rehabilitation, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, 405 30, Gothenburg, Sweden

    Milos Pekny & Marcela Pekna

  2. Florey Institute of Neuroscience and Mental Health, Parkville, VIC, Australia

    Milos Pekny & Marcela Pekna

  3. University of Newcastle, New South Wales, Australia

    Milos Pekny & Marcela Pekna

  4. Waisman Center, University of Wisconsin-Madison, 1500 Highland Avenue, Madison, WI, 53705, USA

    Albee Messing

  5. Medical faculty, Institute of Cellular Neurosciences, University of Bonn, Bonn, Germany

    Christian Steinhäuser

  6. Department of Neurology, The Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, USA

    Jin-Moo Lee

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

    Vladimir Parpura

  8. Department of Translational Neuroscience, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands

    Elly M. Hol

  9. Netherlands Institute for Neuroscience, An Institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam, The Netherlands

    Elly M. Hol

  10. Swammerdam Institute for Life Sciences, Center for Neuroscience, University of Amsterdam, Amsterdam, The Netherlands

    Elly M. Hol

  11. Department of Neurobiology, University of California, Los Angeles, CA, 90095, USA

    Michael V. Sofroniew

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

    Alexei Verkhratsky

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

    Alexei Verkhratsky

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

    Alexei Verkhratsky

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

    Alexei Verkhratsky

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  1. Milos Pekny
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Correspondence to Milos Pekny or Alexei Verkhratsky.

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Pekny, M., Pekna, M., Messing, A. et al. Astrocytes: a central element in neurological diseases. Acta Neuropathol 131, 323–345 (2016). https://doi.org/10.1007/s00401-015-1513-1

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