Persistent NRG1 type III overexpression in spinal motor neurons has no therapeutic effect on ALS‑related pathology in SOD1G93A mice

dc.contributor.authorHernández i Estanyol, Sara
dc.contributor.authorSalvany, Sara
dc.contributor.authorCasanovas i Llorens, Anna
dc.contributor.authorPiedrafita Llorens, Lídia
dc.contributor.authorSoto-Bernardini, María Clara
dc.contributor.authorTarabal Mostazo, Olga
dc.contributor.authorBlasco Carmona, Alba
dc.contributor.authorGras Artells, Sílvia
dc.contributor.authorGatius, Alaó
dc.contributor.authorSchwab, Markus H.
dc.contributor.authorCalderó i Pardo, Jordi
dc.contributor.authorEsquerda Colell, Josep
dc.date.accessioned2023-09-26T07:40:33Z
dc.date.available2023-09-26T07:40:33Z
dc.date.issued2023-04-05
dc.date.updated2023-09-26T07:40:33Z
dc.description.abstractAmyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease affecting upper and lower motor neurons (MNs). Neuregulin-1 (NRG1) is a pleiotropic growth factor that has been shown to be potentially valuable for ALS when supplemented by means of viral-mediated gene therapy. However, these results are inconsistent with other reports. An alternative approach for investigating the therapeutic impact of NRG1 on ALS is the use of transgenic mouse lines with genetically defined NRG1 overexpression. Here, we took advantage of a mouse line with NRG1 type III overexpression in spinal cord α motor neurons (MN) to determine the impact of steadily enhanced NRG1 signalling on mutant superoxide dismutase 1 (SOD1)-induced disease. The phenotype of SOD1G93A-NRG1 double transgenic mice was analysed in detail, including neuropathology and extensive behavioural testing. At least 3 animals per condition and sex were histopathologically assessed, and a minimum of 10 mice per condition and sex were clinically evaluated. The accumulation of misfolded SOD1 (mfSOD1), MN degeneration, and a glia-mediated neuroinflammatory response are pathological hallmarks of ALS progression in SOD1G93A mice. None of these aspects was significantly improved when examined in double transgenic NRG1- SOD1G93A mice. In addition, behavioural testing revealed that NRG1 type III overexpression did not affect the survival of SOD1G93A mice but accelerated disease onset and worsened the motor phenotype.
dc.description.sponsorshipOpen Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature. This work was supported by grants from the Ministerio de Ciencia e Innovación/FEDER (grant number: PID2021-122785OB-I00 (JC and OT)) and the Marató de TV3 Foundation (grant number: 202005-30 [JC]). A.G. holds a predoctoral fellowship from the Universitat de Lleida and Banco Santander.
dc.format.mimetypeapplication/pdf
dc.identifier.doihttps://doi.org/10.1007/s13311-023-01424-x
dc.identifier.idgrec033463
dc.identifier.issn1933-7213
dc.identifier.urihttps://repositori.udl.cat/handle/10459.1/464039
dc.language.isoeng
dc.publisherSpringer
dc.relationinfo:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica, Técnica y de Innovación 2021-2023/PID2021-122785OB-I00/ES/
dc.relation.isformatofReproducció del document publicat a: https://doi.org/10.1007/s13311-023-01424-x
dc.relation.ispartofNeurotherapeutics, 2023 [ ahead of print]
dc.rightscc-by (c) The Authors, 2023
dc.rights.accessRightsinfo:eu-repo/semantics/openAccess
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectAmyotrophic lateral sclerosis
dc.subjectNeuregulin-1
dc.subjectmotor neuron
dc.subjectSOD1
dc.subjectTherapy
dc.subjectAmyotrophic lateral sclerosis
dc.subjectALS
dc.subjectNeuregulin
dc.subjectNRG1
dc.subjectMotor neuron
dc.subjectSOD1
dc.subjectTherapy
dc.titlePersistent NRG1 type III overexpression in spinal motor neurons has no therapeutic effect on ALS‑related pathology in SOD1G93A mice
dc.typeinfo:eu-repo/semantics/article
dc.type.versioninfo:eu-repo/semantics/publishedVersion
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