title: Glutamate and ATP at the Interface Between Signaling and Metabolism in Astroglia: Examples from Pathology.
abstract: Glutamate is the main excitatory transmitter in the brain, while ATP represents the most important energy currency in any living cell. Yet, these chemicals play an important role in both processes, enabling them with dual-acting functions in metabolic and intercellular signaling pathways. Glutamate can fuel ATP production, while ATP can act as a transmitter in intercellular signaling. We discuss the interface between glutamate and ATP in signaling and metabolism of astrocytes. Not only do glutamate and ATP cross each other's paths in physiology of the brain, but they also do so in its pathology. We present the fabric of this process in (patho)physiology through the discussion of synthesis and metabolism of ATP and glutamate in astrocytes as well as by providing a general description of astroglial receptors for these molecules along with the downstream signaling pathways that may be activated. It is astroglial receptors for these dual-acting molecules that could hold a key for medical intervention in pathological conditions. We focus on two examples disclosing the role of activation of astroglial ATP and glutamate receptors in pathology of two kinds of brain tissue, gray matter and white matter, respectively. Interventions at the interface of metabolism and signaling show promise for translational medicine.
authors.affiliation: Department of Neurobiology, Center for Glial Biology in Medicine, Atomic Force Microscopy and Nanotechnology Laboratories, Civitan International Research Center, Evelyn F. McKnight Brain Institute, University of Alabama at Birmingham, 1719 6th Avenue South, CIRC 429, Birmingham, AL, 35294, USA. vlad@uab.edu.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Parpura
authors.affiliation: Department of Cellular and Structural Biology, University of Texas Health Science Center San Antonio, San Antonio, TX, 78229, USA.
authors.forename: Elizabeth S
authors.initials: ES
authors.lastname: Fisher
authors.affiliation: Department of Cellular and Structural Biology, University of Texas Health Science Center San Antonio, San Antonio, TX, 78229, USA.
authors.forename: James D
authors.initials: JD
authors.lastname: Lechleiter
authors.affiliation: Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, 2100, Copenhagen, Denmark.
authors.forename: Arne
authors.initials: A
authors.lastname: Schousboe
authors.affiliation: Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, 2100, Copenhagen, Denmark.
authors.forename: Helle S
authors.initials: HS
authors.lastname: Waagepetersen
authors.affiliation: Department of Neurosciences, Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, OH, 44195, USA.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Brunet
authors.affiliation: Department of Neurosciences, Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, OH, 44195, USA.
authors.forename: Selva
authors.initials: S
authors.lastname: Baltan
authors.affiliation: Faculty of Life Sciences, The University of Manchester, Manchester, M13 9PT, UK.|Achucarro Center for Neuroscience, IKERBASQUE, Basque Foundation for Science, 48011, Bilbao, Spain.|Department of Neurosciences, University of the Basque Country UPV/EHU, 48940, Leioa, Spain.
authors.forename: Alexei
authors.initials: A
authors.lastname: Verkhratsky
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D001253:Astrocytes / Q000378:metabolism* / Q000473:pathology*; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans; D017470:Receptors, Glutamate / Q000378:metabolism*; D011983:Receptors, Purinergic / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D017470:Receptors, Glutamate; D011983:Receptors, Purinergic; D018698:Glutamic Acid; D000255:Adenosine Triphosphate
keywords: Astrocytes; Brain ischemia; Mitochondrion; Neurons; Neurotransmitters; Receptors