Flagship projects

Exploring the role of the embryonic Cavβ1 protein in nerve-muscle reconnection after nerve injury

Embryonic Cavβ1 and repair of the neuromuscular junction 

Sestina Falcone, PhD

The project examines the role of an embryonic variant of a muscle protein, Cavβ1E, which is re-expressed in adult muscle when the muscle is weakened, in particular after nerve damage. This protein, essential to the development of the neuromuscular junction, may also play a major role in maintaining and repairing that junction in adults. 

Scientific challenge

The neuromuscular junction is the structure through which the nerve controls the muscle. When it is impaired (ageing, immobilisation, neuromuscular disease, nerve injury), the muscle loses mass and function. Understanding how Cavβ1E helps preserve this connection could open the way to new strategies to limit muscle loss, improve recovery after nerve damage and gain a better understanding of the fundamental mechanisms that maintain muscle function.

Key questions to unravel

The work aims to determine: 

  • how Cavβ1E influences the repair of the neuromuscular junction after nerve injury; 
  • which proteins and genes interact with this embryonic variant; 
  • which biological mechanisms it controls in adult muscle; 
  • how its absence or its overexpression alters muscle recovery.

The aim is to map a still largely unknown network of players involved in maintaining the neuromuscular system.

Scientific and methodological approach

The researchers will use: 

  • viral vectors to increase or suppress the expression of Cavβ1E in mouse muscles; 
  • a model of transient nerve injury to observe repair of the neuromuscular junction depending on whether the protein is present or absent; 
  • measurements of nerve-muscle connectivity, of muscle strength, and detailed analyses by microscopy; 
  • molecular biology approaches to identify the protein and genetic partners of Cavβ1E.

This work relies on close collaboration between researchers, engineers and specialists in muscle physiology. 

Muscles need a permanent connection with the nerves in order to work properly. We are studying a recently discovered protein that appears to play an essential role in maintaining and repairing this connection. Our aim is to better understand how it works, in order to identify new therapeutic avenues against the loss of muscle mass and function.

Sestina Falcone, PhD, researcher at the Center of Research in Myology, Institute of Myology

Expected impact on research and clinical practice

A better understanding of the role of Cavβ1E could: 

  • explain why some muscles recover better than others after nerve damage; 
  • reveal new therapeutic targets for preserving muscle mass; 
  • open the way to strategies aimed at strengthening the neuromuscular junction in ageing, sarcopenia or certain neuromuscular diseases; 
  • contribute to more personalised medicine, centred on the mechanisms that maintain muscle function. 

This knowledge could benefit a wide range of situations in which the neuromuscular junction is weakened, well beyond a single disease.