Regulation of Duchenne muscular dystrophy through the obestatin/GPR39 system

• Autores: Fátima Fernández Barreiro
• Directores de la Tesis: Icía Santos Zas (dir. tes.), Jesús Pérez Camiña (dir. tes.)
• Lectura: En la Universidade de Santiago de Compostela ( España ) en 2025
• Idioma: inglés
• Tribunal Calificador de la Tesis: Amelia Aranega Jiménez (presid.), Rosalía Gallego Gómez (secret.), Juan Manuel Fernández Costa (voc.)
• Programa de doctorado: Programa Oficial de Doctorado en Endocrinología
• Materias:
  • Química
    • Bioquímica
      • Biología molecular
  • Ciencias de la vida
    • Biología celular
      • Citología
  • Ciencias médicas
    • Ciencias clínicas
      • Patología clínica
    • Medicina interna
      • Endocrinología
• Enlaces
  • Tesis en acceso abierto en: MINERVA
• Resumen

  • Little is known about the mechanisms by which the impairment of autophagy, and related signals, are influenced by stressors connected to Duchenne muscular dystrophy (DMD).

    In this work, we describe the unexpected finding whereby in the dystrophin-deficient mdx mice and in human immortalized DMD myotubes, the obestatin/GPR39 system activates mTOR concurrently with AMPK to control protein synthesis, ubiquitin-proteasome system, and autophagy-lysosome system; counteracting muscle wasting in DMD. The E3 ligase NEDD4-L, is postulated as the major trigger to activate the autophagy process in response to obestatin.

    This study indicates that restoration of autophagy alleviates the symptoms of DMD and supports that obestatin may have potential therapeutic applications for muscular dystrophies.