دورية أكاديمية
Sunitinib-mediated inhibition of STAT3 in skeletal muscle and spinal cord does not affect the disease in a mouse model of ALS.
| العنوان: | Sunitinib-mediated inhibition of STAT3 in skeletal muscle and spinal cord does not affect the disease in a mouse model of ALS. |
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| المؤلفون: | Tortarolo, Massimo, Re Cecconi, Andrea David, Camporeale, Laura, Margotta, Cassandra, Nardo, Giovanni, Pasetto, Laura, Bonetto, Valentina, Galbiati, Mariarita, Crippa, Valeria, Poletti, Angelo, Piccirillo, Rosanna, Bendotti, Caterina |
| المصدر: | Neurobiol Dis ; ISSN:1095-953X ; Volume:199 |
| بيانات النشر: | Elsevier Science |
| سنة النشر: | 2024 |
| المجموعة: | PubMed Central (PMC) |
| مصطلحات موضوعية: | Amyotrophic lateral sclerosis, Atrogenes, Disease progression, Genetic background, SOD1, STAT3, muscle atrophy, Spinal cord, Sunitinib |
| الوصف: | Variability in disease onset and progression is a hallmark of amyotrophic lateral sclerosis (ALS), both in sporadic and genetic forms. Recently, we found that SOD1-G93A transgenic mice expressing the same amount of mutant SOD1 but with different genetic backgrounds, C57BL/6JOlaHsd and 129S2/SvHsd, show slow and rapid muscle wasting and disease progression, respectively. Here, we investigated the different molecular mechanisms underlying muscle atrophy. Although both strains showed similar denervation-induced degradation of muscle proteins, only the rapidly progressing mice exhibited early and sustained STAT3 activation that preceded atrophy in gastrocnemius muscle. We therefore investigated the therapeutic potential of sunitinib, a tyrosine kinase inhibitor known to inhibit STAT3 and prevent cancer-induced muscle wasting. Although sunitinib treatment reduced STAT3 activation in the gastrocnemius muscle and lumbar spinal cord, it did not preserve spinal motor neurons, improve neuromuscular impairment, muscle atrophy and disease progression in the rapidly progressing SOD1-G93A mice. Thus, the effect of sunitinib is not equally positive in different diseases associated with muscle wasting. Moreover, given the complex role of STAT3 in the peripheral and central compartments of the neuromuscular system, the present study suggests that its broad inhibition may lead to opposing effects, ultimately preventing a potential positive therapeutic action in ALS. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | https://doi.org/10.1016/j.nbd.2024.106576Test; https://pubmed.ncbi.nlm.nih.gov/38914173Test |
| DOI: | 10.1016/j.nbd.2024.106576 |
| الإتاحة: | https://doi.org/10.1016/j.nbd.2024.106576Test https://pubmed.ncbi.nlm.nih.gov/38914173Test |
| حقوق: | Copyright © 2024. Published by Elsevier Inc. |
| رقم الانضمام: | edsbas.BEF666E5 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1016/j.nbd.2024.106576 |
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