Ubiquitination Insight from Spinal Muscular Atrophy-From Pathogenesis to Therapy: A Muscle Perspective.

Autor: Bolado-Carrancio A; Departamento de Biología Molecular, Facultad de Medicina, Universidad de Cantabria-and Instituto de Investigación Marqués de Valdecilla (IDIVAL), 39011 Santander, Spain., Tapia O; Departamento de Ciencias Médicas Básicas, Instituto de Tecnologías Biomédicas, Universidad de la Laguna, 38200 La Laguna, Spain., Rodríguez-Rey JC; Departamento de Biología Molecular, Facultad de Medicina, Universidad de Cantabria-and Instituto de Investigación Marqués de Valdecilla (IDIVAL), 39011 Santander, Spain.
Jazyk: angličtina
Zdroj: International journal of molecular sciences [Int J Mol Sci] 2024 Aug 13; Vol. 25 (16). Date of Electronic Publication: 2024 Aug 13.
DOI: 10.3390/ijms25168800
Abstrakt: 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 SMNΔ7. Structural differences between SMN and SMNΔ7 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.
Databáze: MEDLINE
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