Fragment C of tetanus toxin, more than a carrier. Novel perspectives in non-viral ALS gene therapy.

Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte
María Moreno-IgoaRosario Osta Pinzolas

Abstract

The non-toxic carboxy-terminal fragment of tetanus toxin heavy chain (TTC) has been implicated in the activation of cascades responsible for trophic actions and neuroprotection by inhibition of apoptosis. Previous in vitro studies have described signalling pathways that underlie the administration of TTC to neurons. We investigated whether these properties were maintained in a mouse model of neurodegenerative disease. Naked DNA encoding for TTC was injected intramuscularly and neuromuscular function and clinical behaviour were monitored until endstage in the transgenic SOD1G93A mouse model that expresses a mutant variant of human superoxide dismutase 1 (SOD1). Our results indicate that TTC treatment ameliorated the decline of hindlimb muscle innervation, significantly delayed the onset of symptoms and functional deficits, improved spinal motor neuron survival, and prolonged lifespan. Furthermore, we found that caspase-1 and caspase-3 proapoptotic genes were down-regulated in the spinal cord of treated mice. Western blot analysis showed that the active form of caspase-3 was also down-regulated after TTC treatment and survival signals, such as the significant phosphorylation of serine/threonine protein kinase Akt, were also detec...Continue Reading

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References

Mar 23, 1990·Science·J A WolffP L Felgner
Apr 1, 1990·Infection and Immunity·J L HalpernS Stibitz
Aug 12, 1981·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·S McHanwell, T J Biscoe
Jan 1, 1996·Neurobiology of Aging·E VerdúX Navarro
May 2, 1997·The Journal of Biological Chemistry·J S MoyersC R Kahn
Aug 19, 1997·Proceedings of the National Academy of Sciences of the United States of America·L CoenP Brûlet
Jul 23, 2005·Amyotrophic Lateral Sclerosis and Other Motor Neuron Disorders : Official Publication of the World Federation of Neurology, Research Group on Motor Neuron Diseases·Francisco J Miana-MenaRosario Osta
Aug 16, 2006·Neuro-degenerative Diseases·Francisco J Miana-MenaRosario Osta
Apr 1, 2009·Journal of Neurotrauma·Clara PenasXavier Navarro

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Citations

Sep 1, 2012·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Renzo MancusoXavier Navarro
Mar 23, 2011·Orphanet Journal of Rare Diseases·Ana C CalvoRosario Osta
Jul 28, 2012·International Journal of Molecular Sciences·Ana C CalvoRosario Osta
Nov 10, 2011·Toxins·Janne M ToivonenRosario Osta
Aug 27, 2014·BioMed Research International·Ana C CalvoRosario Osta
Jul 8, 2011·Brain Research·Renzo MancusoXavier Navarro
Mar 1, 2011·Clinical Neurophysiology : Official Journal of the International Federation of Clinical Neurophysiology·Renzo MancusoXavier Navarro
Dec 10, 2015·Frontiers in Cellular Neuroscience·Amilia JeyachandranCassie S Mitchell
Mar 6, 2016·The International Journal of Neuropsychopharmacology·Liliana MendietaRosario Moratalla
Mar 20, 2012·Amyotrophic Lateral Sclerosis : Official Publication of the World Federation of Neurology Research Group on Motor Neuron Diseases·Renzo MancusoXavier Navarro
Feb 20, 2013·Toxicon : Official Journal of the International Society on Toxinology·O RossettoC Montecucco
Jul 4, 2016·European Journal of Medicinal Chemistry·Vijay KumarFaizan Ahmad
Mar 15, 2018·Developmental Neuroscience·Adrienne M AntonsonRodney W Johnson
Mar 7, 2013·Nature Reviews. Neuroscience·Wim Robberecht, Thomas Philips
May 30, 2020·Experimental Physiology·Bilal A MirVictoria C Foletta
Jul 23, 2013·Amyotrophic Lateral Sclerosis & Frontotemporal Degeneration·UNKNOWN ALSUntangled Group
Aug 26, 2017·Molecular Neurobiology·Pilar LarrodéRosario Osta
May 21, 2020·Toxins·Laura Moreno-MartinezRosario Osta
Jun 13, 2018·BMC Biotechnology·Yasuhiro WatanabeKenji Nakashima
Nov 10, 2018·Scientific Reports·Citlalli Netzahualcoyotzi, Ricardo Tapia

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