Ubiquitination insight from spinal muscular atrophy-from pathogenesis to therapy: a muscle perspective
Spinal muscular atrophy (SMA) is one of the most frequent causes of death in childhood. The disease's molecular basis is deletion or mutations in the SMN1 gene, which produces reduced survival motor neuron protein (SMN) levels. As a result, there is spinal motor neuron degeneration and a large...
| Autores: | , , |
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| Formato: | artículo |
| Fecha de publicación: | 2024 |
| País: | España |
| Recursos: | Universidad de Cantabria (UC) |
| Repositorio: | UCrea Repositorio Abierto de la Universidad de Cantabria |
| Idioma: | inglés |
| OAI Identifier: | oai:repositorio.unican.es:10902/34590 |
| Acesso em linha: | https://hdl.handle.net/10902/34590 |
| Access Level: | acceso abierto |
| Palavra-chave: | Spinal muscular atrophy Ubiquitin–proteasome system SMN Skeletal muscle atrophy |
| Resumo: | Spinal muscular atrophy (SMA) is one of the most frequent causes of death in childhood. The disease's molecular basis is deletion or mutations in the SMN1 gene, which produces reduced survival motor neuron protein (SMN) levels. As a result, there is spinal motor neuron degeneration and a large increase in muscle atrophy, in which the ubiquitin-proteasome system (UPS) plays a significant role. In humans, a paralogue of SMN1, SMN2 encodes the truncated protein SMN∆7. Structural differences between SMN and SMN∆7 affect the interaction of the proteins with UPS and decrease the stability of the truncated protein. SMN loss affects the general ubiquitination process by lowering the levels of UBA1, one of the main enzymes in the ubiquitination process. We discuss how SMN loss affects both SMN stability and the general ubiquitination process, and how the proteins involved in ubiquitination could be used as future targets for SMA treatment. |
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