Muscle-specific Bet1L knockdown induces neuromuscular denervation, motor neuron degeneration, and motor dysfunction in a rat model of familial ALS DOI Creative Commons

Adam Eckardt,

Claude Marblé,

Bethany Fern

и другие.

Frontiers in Neuroscience, Год журнала: 2025, Номер 19

Опубликована: Янв. 17, 2025

Amyotrophic lateral sclerosis (ALS) is a neuromuscular disease characterized by specific loss of motor neurons in the spinal cord and brain stem. Although ALS has historically been as neuron disease, there evidence that degenerate retrograde manner, beginning periphery at junctions (NMJs) skeletal muscle. We recently reported vesicle trafficking protein Bet1L (Bet1 Golgi Vesicular Membrane Trafficking Protein Like) new molecule possibly linked to NMJ degeneration ALS. In this study, we tested hypothesis gene silencing muscle could influence integrity, function, survival rat model familial (SOD1G93A transgenic). Small interfering RNA (siRNA) targeting was injected on weekly basis into hindlimb pre-symptomatic wild-type (WT) rats. After 3 weeks, intramuscular siRNA injection significantly increased number denervated NMJs knockdown decreased size lumbar cord, which innervated siRNA-injected hindlimb. Impaired function identified hindlimbs Notably, effects were more significant rats when compared WT Together, induces denervation NMJs, but also accelerates progression Our results provide support potential roles key maintenance pathogenesis.

Язык: Английский

Muscle-specific Bet1L knockdown induces neuromuscular denervation, motor neuron degeneration, and motor dysfunction in a rat model of familial ALS DOI Creative Commons

Adam Eckardt,

Claude Marblé,

Bethany Fern

и другие.

Frontiers in Neuroscience, Год журнала: 2025, Номер 19

Опубликована: Янв. 17, 2025

Amyotrophic lateral sclerosis (ALS) is a neuromuscular disease characterized by specific loss of motor neurons in the spinal cord and brain stem. Although ALS has historically been as neuron disease, there evidence that degenerate retrograde manner, beginning periphery at junctions (NMJs) skeletal muscle. We recently reported vesicle trafficking protein Bet1L (Bet1 Golgi Vesicular Membrane Trafficking Protein Like) new molecule possibly linked to NMJ degeneration ALS. In this study, we tested hypothesis gene silencing muscle could influence integrity, function, survival rat model familial (SOD1G93A transgenic). Small interfering RNA (siRNA) targeting was injected on weekly basis into hindlimb pre-symptomatic wild-type (WT) rats. After 3 weeks, intramuscular siRNA injection significantly increased number denervated NMJs knockdown decreased size lumbar cord, which innervated siRNA-injected hindlimb. Impaired function identified hindlimbs Notably, effects were more significant rats when compared WT Together, induces denervation NMJs, but also accelerates progression Our results provide support potential roles key maintenance pathogenesis.

Язык: Английский

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