Acta neuropathologica communications · 2025
Kv3 channel agonist ameliorates the phenotype of a mouse model of amyotrophic lateral sclerosis.
СтатьяНазвание и аннотация: Перевод в очереди
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Marabita Manuela, Marchioretti Caterina, Aravamudhan Aishwarya, Zito Simona, Falconieri Antonella, Zuccaro Emanuela, Andreotti Roberta, Gambarotto Lisa, Metti Samuele, Tonellato Marika, Adami Valentina, Park Kyung Ho, Gunthorpe Martin J, Large Charles H, Marasco Agostino, Vianello Sara, Rosati Jessica, Belluzzi Elisa, Pozzuoli Assunta, Biz Carlo, Ruggieri Pietro, Basso Manuela, Poletti Angelo, Alvaro Giuseppe, Sorarù Gianni, Bonaldo Paolo, Rossetto Ornella, Pilati Nadia, Pennuto Maria
Аннотация
Voltage-gated potassium channels, Kv3.1, Kv3.2, Kv3.3, and Kv3.4, facilitate rapid repolarization and shape action potentials, which are crucial to maintaining high-frequency firing. Little is known about the expression and function of Kv3 channels in skeletal muscle. We show that these channels are expressed in type IIa/IIx fibers, and their transcript levels progressively increase from postnatal age to adulthood in physiological context. In mature myofibers, the Kv3.1 and Kv3.4 channels are enriched in the muscle triads. The expression of the Kv3 channel is lost upon acute motor unit damage, in mouse models of amyotrophic lateral sclerosis (ALS) and spinal and bulbar muscular atrophy (SBMA), and the skeletal muscle of patients with sporadic ALS. Early treatment of ALS and SBMA mice with AUT00201, a positive allosteric modulator of Kv3 channels, improved the phenotype of ALS mice specifically, suggesting that positive modulation of Kv3 channels is a novel therapeutic option for patients with ALS.