Beyond Motor Neurons in Spinal Muscular Atrophy: A Focus on Neuromuscular Junction

• Published in: International journal of molecular sciences Vol. 25; no. 13; p. 7311
• Main Authors: Torri, Francesca, Mancuso, Michelangelo, Siciliano, Gabriele, Ricci, Giulia
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 03-07-2024
• Subjects: Animals; Atrophy; Biomarkers; Clinical trials; Congenital diseases; Denervation; Disease; Disease Models, Animal; Fatigue; Genetic engineering; Humans; Hypotheses; Mice; Motor Neurons - metabolism; Motor Neurons - pathology; Muscular Atrophy, Spinal - genetics; Muscular Atrophy, Spinal - metabolism; Muscular Atrophy, Spinal - pathology; Mutation; Myasthenia gravis; Neuromuscular diseases; neuromuscular junction; Neuromuscular Junction - metabolism; Neuromuscular Junction - pathology; Neurons; Pathogenesis; Pediatrics; Proteins; pyridostigmine; salbutamol; SMA; Survival of Motor Neuron 1 Protein - genetics; Survival of Motor Neuron 1 Protein - metabolism; therapy; salbutamol; fatigue; pyridostigmine; neuromuscular junction; SMA; therapy
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms25137311

5q-Spinal muscular atrophy (5q-SMA) is one of the most common neuromuscular diseases due to homozygous mutations in the
gene. This leads to a loss of function of the
gene, which in the end determines lower motor neuron degeneration. Since the generation of the first mouse models of SMA neuropathology, a complex degenerative involvement of the neuromuscular junction and peripheral axons of motor nerves, alongside lower motor neurons, has been described. The involvement of the neuromuscular junction in determining disease symptoms offers a possible parallel therapeutic target. This narrative review aims at providing an overview of the current knowledge about the pathogenesis and significance of neuromuscular junction dysfunction in SMA, circulating biomarkers, outcome measures and available or developing therapeutic approaches.