title: Differential neuroprotective effects of 5'-deoxy-5'-methylthioadenosine.
abstract: BACKGROUND
  5'-deoxy-5'-methylthioadenosine (MTA) is an endogenous compound produced through the metabolism of polyamines. The therapeutic potential of MTA has been assayed mainly in liver diseases and, more recently, in animal models of multiple sclerosis. The aim of this study was to determine the neuroprotective effect of this molecule in vitro and to assess whether MTA can cross the blood brain barrier (BBB) in order to also analyze its potential neuroprotective efficacy in vivo.
  
  
  METHODS
  Neuroprotection was assessed in vitro using models of excitotoxicity in primary neurons, mixed astrocyte-neuron and primary oligodendrocyte cultures. The capacity of MTA to cross the BBB was measured in an artificial membrane assay and using an in vitro cell model. Finally, in vivo tests were performed in models of hypoxic brain damage, Parkinson's disease and epilepsy.
  
  
  RESULTS
  MTA displays a wide array of neuroprotective activities against different insults in vitro. While the data from the two complementary approaches adopted indicate that MTA is likely to cross the BBB, the in vivo data showed that MTA may provide therapeutic benefits in specific circumstances. Whereas MTA reduced the neuronal cell death in pilocarpine-induced status epilepticus and the size of the lesion in global but not focal ischemic brain damage, it was ineffective in preserving dopaminergic neurons of the substantia nigra in the 1-methyl-4-phenyl-1,2,3,6-tetrahydro-pyridine (MPTP)-mice model. However, in this model of Parkinson's disease the combined administration of MTA and an A2A adenosine receptor antagonist did produce significant neuroprotection in this brain region.
  
  
  CONCLUSIONS
  MTA may potentially offer therapeutic neuroprotection.
authors.affiliation: Center of Neuroimmunology, Institut d'investigacions Biomèdiques August Pi I Sunyer (IDIBAPS) - Hospital Clinic of Barcelona, Barcelona, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Moreno
authors.affiliation: CIMA, Neurosciences Division, University of Navarra, Pamplona, Spain; Oncology Area, Lung Cancer Unit, Center for Biomedical Research of la Rioja (CIBIR), Logroño, Spain.
authors.forename: Iciar
authors.initials: I
authors.lastname: Lopez
authors.affiliation: Center of Neuroimmunology, Institut d'investigacions Biomèdiques August Pi I Sunyer (IDIBAPS) - Hospital Clinic of Barcelona, Barcelona, Spain.
authors.forename: Begoña
authors.initials: B
authors.lastname: Fernández-Díez
authors.affiliation: Department of Neurosciences, University of Basque Country, Achucarro Basque Center for Neuroscience, Leioa, Spain; Institute of Neurobiology, Slovak Academy of Sciences, Kosice, Slovak Republic.
authors.forename: Miroslav
authors.initials: M
authors.lastname: Gottlieb
authors.affiliation: Department of Neurosciences, University of Basque Country, Achucarro Basque Center for Neuroscience, Leioa, Spain; Institute of Neurobiology, Slovak Academy of Sciences, Kosice, Slovak Republic; Centro de Investigaciones Biomédicas en red en Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Matute
authors.affiliation: Department of Neurosciences, University of Basque Country, Achucarro Basque Center for Neuroscience, Leioa, Spain.
authors.forename: María Victoria
authors.initials: MV
authors.lastname: Sánchez-Gómez
authors.affiliation: Department of Neurosciences, University of Basque Country, Achucarro Basque Center for Neuroscience, Leioa, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Domercq
authors.affiliation: Centro de Investigaciones Biomédicas en red en Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain; Department of Cellular Biology, Immunology and Neurosciences, Medicine School, University of Barcelona, Barcelona, Spain.
authors.forename: Albert
authors.initials: A
authors.lastname: Giralt
authors.affiliation: Centro de Investigaciones Biomédicas en red en Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain; Department of Cellular Biology, Immunology and Neurosciences, Medicine School, University of Barcelona, Barcelona, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Alberch
authors.affiliation: Department of Neurology, University of Michigan Medical Center, Ann Arbor, Michigan, United States of America.
authors.forename: Kevin W
authors.initials: KW
authors.lastname: Collon
authors.affiliation: Department of Neurology, University of Michigan Medical Center, Ann Arbor, Michigan, United States of America.
authors.forename: Helen
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Neurology, University of Michigan Medical Center, Ann Arbor, Michigan, United States of America.
authors.forename: Jack M
authors.initials: JM
authors.lastname: Parent
authors.affiliation: Institute for Research in Biomedicine (IRB), Barcelona, Spain.
authors.forename: Meritxell
authors.initials: M
authors.lastname: Teixido
authors.affiliation: Institute for Research in Biomedicine (IRB), Barcelona, Spain.
authors.forename: Ernest
authors.initials: E
authors.lastname: Giralt
authors.affiliation: Universidad de Castilla la Mancha, Albacete, Spain.
authors.forename: Valentín
authors.initials: V
authors.lastname: Ceña
authors.affiliation: Universidad de Castilla la Mancha, Albacete, Spain.
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Posadas
authors.affiliation: CIMA, Neurosciences Division, University of Navarra, Pamplona, Spain.
authors.forename: Eva
authors.initials: E
authors.lastname: Martínez-Pinilla
authors.affiliation: Center of Neuroimmunology, Institut d'investigacions Biomèdiques August Pi I Sunyer (IDIBAPS) - Hospital Clinic of Barcelona, Barcelona, Spain.
authors.forename: Pablo
authors.initials: P
authors.lastname: Villoslada
authors.affiliation: CIMA, Neurosciences Division, University of Navarra, Pamplona, Spain; Oncology Area, Lung Cancer Unit, Center for Biomedical Research of la Rioja (CIBIR), Logroño, Spain; Department of Neurosciences, University of Basque Country, Achucarro Basque Center for Neuroscience, Leioa, Spain; Institute of Neurobiology, Slovak Academy of Sciences, Kosice, Slovak Republic; Centro de Investigaciones Biomédicas en red en Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain; Department of Cellular Biology, Immunology and Neurosciences, Medicine School, University of Barcelona, Barcelona, Spain; Department of Neurology, University of Michigan Medical Center, Ann Arbor, Michigan, United States of America; Institute for Research in Biomedicine (IRB), Barcelona, Spain; Universidad de Castilla la Mancha, Albacete, Spain; Department of Biochemistry and Molecular Biology, School of Biology, University of Barcelona, Barcelona, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Franco
mesh_terms: D000208:Acute Disease; D018674:Adrenergic Antagonists / Q000494:pharmacology; D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000473:pathology; D002545:Brain Ischemia / Q000188:drug therapy / Q000473:pathology; D002463:Cell Membrane Permeability; D002478:Cells, Cultured; D002908:Chronic Disease; D003839:Deoxyadenosines / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D005947:Glucose / Q000172:deficiency; D008297:Male; D051379:Mice; D016202:N-Methylaspartate / Q000633:toxicity; D009410:Nerve Degeneration / Q000188:drug therapy / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D009498:Neurotoxins / Q000633:toxicity; D010100:Oxygen; D010862:Pilocarpine; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D013226:Status Epilepticus / Q000188:drug therapy / Q000473:pathology; D013872:Thionucleosides / Q000494:pharmacology* / Q000627:therapeutic use; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000633:toxicity
chemical_list: D018674:Adrenergic Antagonists; D003839:Deoxyadenosines; D018696:Neuroprotective Agents; D009498:Neurotoxins; D013872:Thionucleosides; D010862:Pilocarpine; C008500:5'-methylthioadenosine; D016202:N-Methylaspartate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D005947:Glucose; D010100:Oxygen