ALS is a progressively debilitating neurodegenerative disease due to the gradual impairment of motor neurons, the nerve cells that stimulate muscle contraction allowing movement and other important functions. When motor neurons degenerate in patients, voluntary muscles no longer receive stimulation from the brain and atrophy, leading to complete paralysis. Currently, treatments are used to reduce the symptoms of the disease but there is no cure to stop its progression.

Defects in the neuromuscular junction - the connection point between motor neurons and muscle - are among the first hallmarks of ALS.

According to the research, conducted by Alessandro Rosa's group from the Department of Biology and Biotechnology of Sapienza in collaboration with the Italian Institute of Technology (IIT) and the University of Pittsburgh, there is a link between the dysregulation of a specific protein, called HuD, and neuromuscular junction disorders in ALS patients.

"The results obtained identify this protein as playing a crucial role at an early stage of the disease, thus suggesting it as a possible target in the therapeutic field" highlighted Alessandro Rosa.

Research showed how high levels of the HuD protein can lead to defects at the neuromuscular junction resulting in degeneration of motor neurons. Reducing the protein levels with targeted therapies could therefore limit neuromuscular junction disorders in patients.

This evidence was confirmed in vivo in an animal model, the midge Drosophila melanogaster, in which overexpression of the protein causes defects in locomotion, while its reduction improves the motor phenotype.

The project was funded by the PNRR (National Recovery and Resilience Plan) under National Centre 3 - Development of gene therapy and drugs with RNA technology. Alessio Colantoni and Monica Ballarino contributed to the work for the Department of Biology and Biotechnology. 

References:

“HuD impairs neuromuscular junctions and induces apoptosis in human iPSC and Drosophila ALS models” - Beatrice Silvestri, Michela Mochi, Darilang Mawrie, Valeria de Turris, Alessio Colantoni, Beatrice Borhy, Margherita Medici, Eric Nathaniel Anderson, Maria Giovanna Garone, Christopher Patrick Zammerilla, Marco Simula, Monica Ballarino, Udai Bhan Pandey & Alessandro Rosa. Nature Communications, volume 15, Article number: 9618 (2024) doi: https://www.nature.com/articles/s41467-024-54004-8

Further Information

Alessandro Rosa
Department of Biology and Biotechnology Charles Darwin
alessandro.rosa@uniroma1.it