Web of Science: 5 citations, Scopus: 6 citations, Google Scholar: citations,
Neuroprotective Effect of Non-viral Gene Therapy Treatment Based on Tetanus Toxin C-fragment in a Severe Mouse Model of Spinal Muscular Atrophy
Oliván, Sara (Universidad de Zaragoza. Centro de Investigación Biomédica en Red en Bioingeniería, Biomateriales y Nanomedicina. Grupo AMB.)
Calvo, Ana C. (Universidad de Zaragoza. Facultad de Veterinaria. Laboratorio de Genética Bioquímica)
Rando, Amaya (Universidad de Zaragoza. Facultad de Veterinaria. Laboratorio de Genética Bioquímica)
Herrando Grabulosa, Mireia (Universitat Autònoma de Barcelona. Institut de Neurociències)
Manzano, Raquel (University of Oxford. Department of Physiology, Anatomy and Genetics)
Zaragoza, Pilar (Universidad de Zaragoza. Instituto Agroalimentario de Aragón (IA2))
Tizzano, Eduardo F. (Hospital Vall d'Hebron. Àrea de Genètica Clínica i Molecular. Centros de Investigación Biomédica en Red)
Aguilera Ávila, José (Universitat Autònoma de Barcelona. Institut de Neurociències)
Osta, Rosario (Universidad de Zaragoza. Centro de Investigación y Tecnología Agroalimentaria de Aragón)
Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular

Date: 2016
Abstract: Spinal muscular atrophy (SMA) is a hereditary childhood disease that causes paralysis and progressive degeneration of skeletal muscles and spinal motor neurons. SMA is associated with reduced levels of full-length Survival of Motor Neuron (SMN) protein, due to mutations in the Survival of Motor Neuron 1 gene. Nowadays there are no effective therapies available to treat patients with SMA, so our aim was to test whether the non-toxic carboxy-terminal fragment of tetanus toxin heavy chain (TTC), which exhibits neurotrophic properties, might have a therapeutic role or benefit in SMA. In this manuscript, we have demonstrated that TTC enhance the SMN expression in motor neurons “ in vitro ” and evaluated the effect of intramuscular injection of TTC-encoding plasmid in the spinal cord and the skeletal muscle of SMNdelta7 mice. For this purpose, we studied the weight and the survival time, as well as, the survival and cell death pathways and muscular atrophy. Our results showed that TTC treatment reduced the expression of autophagy markers (Becn1, Atg5, Lc3, and p62) and pro-apoptotic genes such as Bax and Casp3 in spinal cord. In skeletal muscle, TTC was able to downregulate the expression of the main marker of autophagy, Lc3, to wild-type levels and the expression of the apoptosis effector protein, Casp3. Regarding the genes related to muscular atrophy (Ankrd1, Calm1, Col19a1, Fbox32, Mt2, Myod1, NogoA, Pax7, Rrad, and Sln), TTC suggest a compensatory effect for muscle damage response, diminished oxidative stress and modulated calcium homeostasis. These preliminary findings suggest the need for further experiments to depth study the effect of TTC in SMA disease.
Note: Número d'acord de subvenció ISCIII/PI14-00947
Rights: Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original. Creative Commons
Language: Anglès.
Document: article ; recerca ; publishedVersion
Subject: Spinal muscular atrophy ; C-terminal fragment of the tetanus toxin ; Muscle ; Spinal cord ; Autophagy ; Apoptosis ; Muscular atrophy
Published in: Frontiers in Molecular Neuroscience, Vol. 9 (August 2016) , art. 76, ISSN 1662-5099

PMID: 27605908
DOI: 10.3389/fnmol.2016.00076


10 p, 3.4 MB

The record appears in these collections:
Research literature > UAB research groups literature > Research Centres and Groups (scientific output) > Health sciences and biosciences > Institut de Neurociències (INc)
Articles > Research articles
Articles > Published articles

 Record created 2018-02-07, last modified 2019-04-13



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