La Sapienza - Università di Roma

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als caused by Muscle/Nerve Communication Error


A new study coordinated by Prof. Antonio Musarò from the Sapienza Department of Anatomical, Histological, Medical-Legal and Locomotor Apparatus Sciences and implemented in collaboration with Fondazione Roma, IIT-Sapienza, Pasteur-Italy Institute and Telethon has identified the molecular mechanism that is responsible for the neuromuscular junction damage that occurs in various pathologies and pathological alterations.

Neuromuscular joints are a functional bridge that facilitates communication between muscles and nerves; in fact, their operation is based on physiological and pathological inputs from the two types of tissue.

In studies conducted so far, which have mainly focused on the identification of pathogenic mechanisms characterized by amyotrophic lateral sclerosis (ALS), however these studies never solved the issue regarding to the neuromuscular junction damage.

The study conducted by Sapienza, which has been published on the international magazine Antioxidant and Redox Signalling, developed an experimental model through which they induced a gene alteration - similar to that experienced by patients with familial ALS - in mice. However, this gene alteration only affected muscles, not motor neurons. The aim was to understand whether an alteration starting in the muscle could compromise the "maintenance" of the neuromuscular junction and muscle-nerve communication.
"We demonstrated,” explains Prof. Musarò “that an alteration of the skeletal muscle induces damage in the neuromuscular junction. We then identified the molecular mechanism behind the damage and found that it depends on the activation of a kinase protein, known as PKC theta." Its pharmacological "silencing" preserves neuromuscular junctions and the maintenance of muscle mass and strength in treated mice.

"Our work,” concludes Musarò, “supports the concept of dying back, so peripheral alteration can lead to the activation of degenerative mechanisms at the primary level in motor neurons, and also proposes a new therapeutic approach to treat ALS and neuromuscular pathologies, triggering a "saving back" process.