Differential neuroprotective effects of 5'-deoxy-5'-methylthioadenosine.

<h4>Background</h4>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 th...

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Autores principales:	Beatriz Moreno, Iciar Lopez, Begoña Fernández-Díez, Miroslav Gottlieb, Carlos Matute, María Victoria Sánchez-Gómez, María Domercq, Albert Giralt, Jordi Alberch, Kevin W Collon, Helen Zhang, Jack M Parent, Meritxell Teixido, Ernest Giralt, Valentín Ceña, Inmaculada Posadas, Eva Martínez-Pinilla, Pablo Villoslada, Rafael Franco
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/375da3cf40494ec0a03f83ee7067971a
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spelling	oai:doaj.org-article:375da3cf40494ec0a03f83ee7067971a2021-11-18T08:29:33ZDifferential neuroprotective effects of 5'-deoxy-5'-methylthioadenosine.1932-620310.1371/journal.pone.0090671https://doaj.org/article/375da3cf40494ec0a03f83ee7067971a2014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24599318/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusion</h4>MTA may potentially offer therapeutic neuroprotection.Beatriz MorenoIciar LopezBegoña Fernández-DíezMiroslav GottliebCarlos MatuteMaría Victoria Sánchez-GómezMaría DomercqAlbert GiraltJordi AlberchKevin W CollonHelen ZhangJack M ParentMeritxell TeixidoErnest GiraltValentín CeñaInmaculada PosadasEva Martínez-PinillaPablo VillosladaRafael FrancoPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 3, p e90671 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Beatriz Moreno Iciar Lopez Begoña Fernández-Díez Miroslav Gottlieb Carlos Matute María Victoria Sánchez-Gómez María Domercq Albert Giralt Jordi Alberch Kevin W Collon Helen Zhang Jack M Parent Meritxell Teixido Ernest Giralt Valentín Ceña Inmaculada Posadas Eva Martínez-Pinilla Pablo Villoslada Rafael Franco Differential neuroprotective effects of 5'-deoxy-5'-methylthioadenosine.
description	<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusion</h4>MTA may potentially offer therapeutic neuroprotection.
format	article
author	Beatriz Moreno Iciar Lopez Begoña Fernández-Díez Miroslav Gottlieb Carlos Matute María Victoria Sánchez-Gómez María Domercq Albert Giralt Jordi Alberch Kevin W Collon Helen Zhang Jack M Parent Meritxell Teixido Ernest Giralt Valentín Ceña Inmaculada Posadas Eva Martínez-Pinilla Pablo Villoslada Rafael Franco
author_facet	Beatriz Moreno Iciar Lopez Begoña Fernández-Díez Miroslav Gottlieb Carlos Matute María Victoria Sánchez-Gómez María Domercq Albert Giralt Jordi Alberch Kevin W Collon Helen Zhang Jack M Parent Meritxell Teixido Ernest Giralt Valentín Ceña Inmaculada Posadas Eva Martínez-Pinilla Pablo Villoslada Rafael Franco
author_sort	Beatriz Moreno
title	Differential neuroprotective effects of 5'-deoxy-5'-methylthioadenosine.
title_short	Differential neuroprotective effects of 5'-deoxy-5'-methylthioadenosine.
title_full	Differential neuroprotective effects of 5'-deoxy-5'-methylthioadenosine.
title_fullStr	Differential neuroprotective effects of 5'-deoxy-5'-methylthioadenosine.
title_full_unstemmed	Differential neuroprotective effects of 5'-deoxy-5'-methylthioadenosine.
title_sort	differential neuroprotective effects of 5'-deoxy-5'-methylthioadenosine.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/375da3cf40494ec0a03f83ee7067971a
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Differential neuroprotective effects of 5'-deoxy-5'-methylthioadenosine.

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