Neuroprotective Effect of Non-viral Gene Therapy Treatment Based on Tetanus Toxin C-fragment in a Severe Mouse Model of Spinal Muscular Atrophy
| العنوان: | Neuroprotective Effect of Non-viral Gene Therapy Treatment Based on Tetanus Toxin C-fragment in a Severe Mouse Model of Spinal Muscular Atrophy |
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| المؤلفون: | Oliván, Sara, Calvo, Ana Cristina, Rando, Amaya, Herrando-Grabulosa, Mireia, Manzano, Raquel, Zaragoza, Pilar, Tizzano, Eduardo F., Aguilera, José, Osta, Rosario, Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular |
| المصدر: | Frontiers in Molecular Neuroscience, Vol 9 (2016) Frontiers in Molecular Neuroscience Dipòsit Digital de Documents de la UAB Universitat Autònoma de Barcelona Zaguán. Repositorio Digital de la Universidad de Zaragoza instname |
| سنة النشر: | 2016 |
| مصطلحات موضوعية: | 0301 basic medicine, ANKRD1, C-terminal fragment of the tetanus toxin, Muscular atrophy, Apoptosis, Biology, Neuroprotection, lcsh:RC321-571, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Atrophy, Tetanus Toxin, medicine, Autophagy, cardiovascular diseases, Molecular Biology, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, Original Research, spinal muscular atrophy, Spinal cord, Skeletal muscle, Survival of motor neuron, Spinal muscular atrophy, Anatomy, medicine.disease, SMA, 030104 developmental biology, medicine.anatomical_structure, Spinal Cord, muscular atrophy, Cancer research, Muscle, c-terminal fragment of the tetanus toxin, 030217 neurology & neurosurgery, Neuroscience |
| الوصف: | 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. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::159201d16e735f1137ee1be7a53e0e29Test https://ddd.uab.cat/record/185972Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....159201d16e735f1137ee1be7a53e0e29 |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |