000056797 001__ 56797
000056797 005__ 20211201113713.0
000056797 0247_ $$2doi$$a10.3389/fnmol.2016.00076
000056797 0248_ $$2sideral$$a96354
000056797 037__ $$aART-2016-96354
000056797 041__ $$aeng
000056797 100__ $$0(orcid)0000-0003-0156-4230$$aOliván, S.$$uUniversidad de Zaragoza
000056797 245__ $$aNeuroprotective effect of non-viral gene therapy treatment based on tetanus toxin C-fragment in a severe mouse model of spinal muscular atrophy
000056797 260__ $$c2016
000056797 5060_ $$aAccess copy available to the general public$$fUnrestricted
000056797 5203_ $$aSpinal 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 TTCencoding 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 proapoptotic 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.
000056797 536__ $$9info:eu-repo/grantAgreement/ES/FIS/PI14-00947
000056797 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000056797 590__ $$a5.076$$b2016
000056797 591__ $$aNEUROSCIENCES$$b42 / 258 = 0.163$$c2016$$dQ1$$eT1
000056797 592__ $$a2.59$$b2016
000056797 593__ $$aMolecular Biology$$c2016$$dQ1
000056797 593__ $$aCellular and Molecular Neuroscience$$c2016$$dQ1
000056797 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000056797 700__ $$0(orcid)0000-0001-5193-7782$$aCalvo, A.C.$$uUniversidad de Zaragoza
000056797 700__ $$0(orcid)0000-0002-2898-4561$$aRando, A.$$uUniversidad de Zaragoza
000056797 700__ $$aHerrando-Grabulosa, M.
000056797 700__ $$0(orcid)0000-0002-7477-8742$$aManzano, R.
000056797 700__ $$0(orcid)0000-0001-5740-0185$$aZaragoza, P.$$uUniversidad de Zaragoza
000056797 700__ $$aTizzano, E.F.
000056797 700__ $$aAquilera, J.
000056797 700__ $$0(orcid)0000-0001-5687-6704$$aOsta, R.$$uUniversidad de Zaragoza
000056797 7102_ $$11001$$2420$$aUniversidad de Zaragoza$$bDpto. Anatom.,Embri.Genét.Ani.$$cÁrea Genética
000056797 7102_ $$11003$$2443$$aUniversidad de Zaragoza$$bDpto. Anatom.Histolog.Humanas$$cArea Histología
000056797 773__ $$g9 (2016), [10 pp]$$pFront. mol. neurosci.$$tFrontiers in molecular neuroscience$$x1662-5099
000056797 8564_ $$s3530745$$uhttps://zaguan.unizar.es/record/56797/files/texto_completo.pdf$$yVersión publicada
000056797 8564_ $$s101499$$uhttps://zaguan.unizar.es/record/56797/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
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000056797 951__ $$a2021-12-01-11:34:03
000056797 980__ $$aARTICLE