Muscle Expression of SOD1G93A Triggers the Dismantlement of Neuromuscular Junction via PKC-Theta.

Bianca Maria Scicchitano, Gabriella Dobrowolny, Martina Martini, Vanina Romanello, Simona Boncompagni, Carmine Nicoletti, Laura Pietrangelo, Simone De Panfilis, Angela Catizone, Marina Bouchè, Marco Sandri, Rüdiger Rudolf, Feliciano Protasi, Antonio Musarò

Risultato della ricerca: Contributo in rivistaArticolo in rivista

23 Citazioni (Scopus)

Abstract

AIM: Neuromuscular junction (NMJ) represents the morphofunctional interface between muscle and nerve. Several chronic pathologies such as aging and neurodegenerative diseases, including muscular dystrophy and amyotrophic lateral sclerosis, display altered NMJ and functional denervation. However, the triggers and the molecular mechanisms underlying the dismantlement of NMJ remain unclear. RESULTS: Here we provide evidence that perturbation in redox signaling cascades, induced by muscle-specific accumulation of mutant SOD1G93A in transgenic MLC/SOD1G93A mice, is causally linked to morphological alterations of the neuromuscular presynaptic terminals, high turnover rate of acetylcholine receptor, and NMJ dismantlement. The analysis of potential molecular mechanisms that mediate the toxic activity of SOD1G93A revealed a causal link between protein kinase Cθ (PKCθ) activation and NMJ disintegration. INNOVATION: The study discloses the molecular mechanism that triggers functional denervation associated with the toxic activity of muscle SOD1G93A expression and suggests the possibility of developing a new strategy to counteract age- and pathology-associated denervation based on pharmacological inhibition of PKCθ activity. CONCLUSIONS: Collectively, these data indicate that muscle-specific accumulation of oxidative damage can affect neuromuscular communication and induce NMJ dismantlement through a PKCθ-dependent mechanism. Antioxid. Redox Signal. 00, 000-000.
Lingua originaleEnglish
pagine (da-a)N/A-N/A
RivistaANTIOXIDANTS & REDOX SIGNALING
DOI
Stato di pubblicazionePubblicato - 2018

Keywords

  • ALS
  • aging

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