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Title: Differential neuroprotective effects of 5'-deoxy-5'-methylthioadenosine
Author: Moreno, Beatriz
López, Iciar
Fernández-Díez, Begoña
Gottlieb, Miroslav
Matute, Carlos
Sánchez-Gómez, María Victoria
Domercq, María
Giralt Coll, Albert
Alberch i Vié, Jordi
Collon, Kevin W.
Zhang, Helen
Parent, Jack M.
Teixidó Turà, Meritxell
Giralt Lledó, Ernest
Ceña, Valentín
Posadas, Inmaculada
Martínez-Pinilla, Eva
Villoslada, Pablo
Franco Fernández, Rafael
Keywords: Poliamines
Malalties del fetge
Malalties del sistema nerviós
Liver diseases
Nervous System Diseases
Issue Date: Mar-2014
Publisher: Public Library of Science (PLoS)
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-pyr​idine(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. Conclusion MTA may potentially offer therapeutic neuroprotection.
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It is part of: PLoS One, 2014, vol. 9, num. 3, p. e90671
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ISSN: 1932-6203
Appears in Collections:Articles publicats en revistes (Institut de Recerca Biomèdica (IRB Barcelona))
Articles publicats en revistes (Bioquímica i Biomedicina Molecular)

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