Muscle resilience: the role of CtBP1 protein
When nerves disconnect from muscles, after injury, or in disease and aging, muscle tissue deteriorates rapidly. Understanding how muscle fibers maintain or lose their identity following denervation is crucial for developing new treatments for neuromuscular diseases and injuries.
CtBP1 responds rapidly to denervation
The research team led by Prof. Perrine Castets investigated what are the roles of the CtBP1 protein in healthy and denervated skeletal muscles. In their recent study published in Skeletal Muscle, they found that CtBP1 accumulates in muscle cell nuclei just two days after nerve injury, suggesting a regulatory role of the protein in the early stages of the muscle response to denervation.
Two days after denervation (bottom panels, in red) CtBP1 strongly accumulates in muscle cell nuclei compared to innervated muscle (top panels) © adapted from Figure 2, Cattaneo et al. 2026 Skeletal Muscle.
A broad impact on gene expression and metabolism
Using mouse models, the team demonstrated that reducing CtBP1 levels disrupts the expression of a wide range of genes. These include not only genes linked to the synaptic machinery, but also genes encoding proteins associated with key metabolic pathways. These molecular changes were accompanied by perturbations in muscle properties, with muscle fibres adopting the characteristics of slower, more oxidative types, with an altered mitochondrial network, which are hallmarks of denervated muscle.
By modulating vast gene networks, CtBP1 helps maintain the metabolic balance of muscles.
Implications for muscle health and disease
The findings identify CtBP1 as an essential component of muscle integrity, helping to preserve the “innervated” state. By counteracting the metabolic and contractile reprogramming induced by denervation, CtBP1 emerges as a promising therapeutic target for conditions associated with a loss of neuromuscular integrity. Further research will be essential to determine whether modulating CtBP1 activity can slow or prevent muscle atrophy and dysfunction in these pathological conditions.