Gene therapy for overexpressing Neuregulin 1 type I in skeletal muscles promotes functional improvement in the SOD1G93A ALS mice
| Autor: | Isaac Francos-Quijorna, Assumpció Bosch, Xavier Navarro, Belén García-Lareu, Ana C. Calvo, Rubèn López-Vales, Rosario Osta, Sergi Verdés, Guillem Mòdol-Caballero, Neus Solanes, Mireia Herrando-Grabulosa |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Gene isoform Genetically modified mouse Neuromuscular junction lcsh:RC321-571 03 medical and health sciences 0302 clinical medicine mental disorders Neuregulin 1 Medicine Amyotrophic lateral sclerosis lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry Motor function Spinal cord biology business.industry ErbB receptors Skeletal muscle medicine.disease Cell biology Motoneuron 030104 developmental biology medicine.anatomical_structure Neurology biology.protein business 030217 neurology & neurosurgery Reinnervation |
| Zdroj: | Neurobiology of Disease, Vol 137, Iss, Pp 104793-(2020) |
| Popis: | Altres ajuts: Fundació La Marato-TV3: TV3201428-10 ; AFM-Telethon: 20289 Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder affecting motoneurons (MNs), with no effective treatment currently available. The molecular mechanisms that are involved in MN death are complex and not fully understood, with partial contributions of surrounding glial cells and skeletal muscle to the disease. Neuregulin 1 (NRG1) is a trophic factor highly expressed in MNs and neuromuscular junctions. Recent studies have suggested a crucial role of the isoform I (NRG1-I) in the collateral reinnervation process in skeletal muscle, and NRG1-III in the preservation of MNs in the spinal cord, opening a window for developing novel therapies for neuromuscular diseases like ALS. In this study, we overexpressed NRG1-I widely in the skeletal muscles of the SOD1G93A transgenic mouse. The results show that NRG1 gene therapy activated the survival pathways in muscle and spinal cord, increasing the number of surviving MNs and neuromuscular junctions and reducing the astroglial reactivity in the spinal cord of the treated SOD1G93A mice. Furthermore, NRG1-I overexpression preserved motor function and delayed the onset of clinical disease. In summary, our data indicates that NRG1 plays an important role on MN survival and muscle innervation in ALS, and that viral-mediated overexpression of NRG1 isoforms may be considered as a promising approach for ALS treatment. |
| Databáze: | OpenAIRE |
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