title: Astrocytes: a central element in neurological diseases.
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.
authors.affiliation: 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@neuro.gu.se.|Florey Institute of Neuroscience and Mental Health, Parkville, VIC, Australia. Milos.Pekny@neuro.gu.se.|University of Newcastle, New South Wales, Australia. Milos.Pekny@neuro.gu.se.
authors.forename: Milos
authors.initials: M
authors.lastname: Pekny
authors.affiliation: 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.|Florey Institute of Neuroscience and Mental Health, Parkville, VIC, Australia.|University of Newcastle, New South Wales, Australia.
authors.forename: Marcela
authors.initials: M
authors.lastname: Pekna
authors.affiliation: Waisman Center, University of Wisconsin-Madison, 1500 Highland Avenue, Madison, WI, 53705, USA.
authors.forename: Albee
authors.initials: A
authors.lastname: Messing
authors.affiliation: Medical faculty, Institute of Cellular Neurosciences, University of Bonn, Bonn, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Steinhäuser
authors.affiliation: Department of Neurology, The Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, USA.
authors.forename: Jin-Moo
authors.initials: JM
authors.lastname: Lee
authors.affiliation: 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.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Parpura
authors.affiliation: Department of Translational Neuroscience, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands.|Netherlands Institute for Neuroscience, An Institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam, The Netherlands.|Swammerdam Institute for Life Sciences, Center for Neuroscience, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Elly M
authors.initials: EM
authors.lastname: Hol
authors.affiliation: Department of Neurobiology, University of California, Los Angeles, CA, 90095, USA.
authors.forename: Michael V
authors.initials: MV
authors.lastname: Sofroniew
authors.affiliation: Faculty of Life Sciences, The University of Manchester, Oxford Road, Manchester, M13 9PT, UK. Alexej.Verkhratsky@manchester.ac.uk.|Achucarro Center for Neuroscience, IKERBASQUE, Basque Foundation for Science, 48011, Bilbao, Spain. Alexej.Verkhratsky@manchester.ac.uk.|Department of Neurosciences, University of the Basque Country UPV/EHU and CIBERNED, Leioa, Spain. Alexej.Verkhratsky@manchester.ac.uk.|University of Nizhny Novgorod, Nizhny Novgorod, 603022, Russia. Alexej.Verkhratsky@manchester.ac.uk.
authors.forename: Alexei
authors.initials: A
authors.lastname: Verkhratsky
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000473:pathology*; D002493:Central Nervous System Diseases / Q000473:pathology*; D006801:Humans
keywords: Alexander disease; Alzheimer’s disease; Astrocytes; Astrocytopathies; Astroglial cells; Epilepsy; Huntington disease; Neurological diseases; Neurotrauma; Reactive astrogliosis; Reactive gliosis; Stroke