Skip to main content
Scientific

USC CiMUS research uncovers a new mechanism in diseases that damage the "protective layer" of nerves

  • This finding, published in the international journal Science Advances, provides a solid basis for understanding pathologies such as Charcot-Marie-Tooth disease and multiple sclerosis.

 

There are numerous diseases of the nervous system in which, due to circumstances of unknown origin, the myelin sheath, the fatty material that covers nerve cells, is altered. This is the case with multiple sclerosis or Charcot-Marie-Tooth disease, to name but a few of the most common so-called "demyelinating diseases". How the demyelination mechanism works and what are the causes that trigger this process are, for the time being, the subject of research. In this context, CiMUS research at the University of Santiago de Compostela (USC) has just discovered a new mechanism that precisely regulates the formation of myelin in peripheral nerves. This finding, published today in the international journal Science Advances, opens the door to a better understanding of how mutations in several genes lead to pathology in Charcot-Marie-Tooth disease, a group of hereditary diseases that can affect the myelin sheaths of peripheral nerves.

The study, conducted by the Regulation of Gene Expression in Disease research group at CiMUS co-led by Ashwin Woodhoo, GAIN researcher Oportunius, and Marta Varela Rey, was led mainly by researchers Paula Ayuso, Alejandro Sánchez-Rueda and Sergio Velasco.

 

Nedylation, key to nerve development and regeneration

The myelin sheath is essential for neuronal function and health. This has been demonstrated by observing nerve defects in genetic mouse models and in the more than 100 genes containing mutations identified in Charcot-Marie-Tooth disease.

"This work opens up new approaches for understanding human nerve pathology and, in particular, inherited demyelinating disorders. There is clear evidence that mutations in several genes encoding critical components of neddylation-regulated pathways are associated with human nerve pathology, and our study provides a platform for understanding the pathogenic mechanisms that may be involved in these cases," explains CiMUS researcher Aswhin Woodhoo.

This study demonstrates that neddylation is essential for the myelination of Schwann cells, which play a critical role in neuronal function and health, as well as nerve development and regeneration. Genetic or pharmacological inhibition of neddylation leads to an arrest of Schwann cells at the promyelin stage, rendering them unable to continue the myelination process.

Defects in myelination led to severe gait abnormalities, muscle weakness and hindlimb impingement, characteristic of neuromuscular dysfunction very early after birth. The researchers also discovered that neddylation plays complex roles in Schwann cells by regulating multiple control mechanisms. This places neddylation as a central regulatory centre driving Schwann cell myelination.

This CiMUS study therefore contributes to understanding the mechanisms involved in diseases in which the "protective layer" of nerves is affected by discovering that neddylation is essential for the development of peripheral nerves, as well as a powerful coordinator of the molecular circuitry that promotes myelination, providing new therapeutic approaches for demyelinating diseases.

Charcot-Marie-Tooth disease

Charcot-Marie-Tooth disease is a group of inherited neurological disorders that cause nerve damage, with the greatest damage to the arms and legs as the peripheral nerves are affected.

It causes smaller and weaker muscles, resulting in loss of sensation and muscle contractions and difficulty walking.  Foot deformities such as hammertoes and high plantar arches are also common in this disease.

Symptoms usually begin in the feet and legs, eventually spreading to the hands and arms. They usually manifest in adolescence, although they can also appear in early adulthood or middle age.
 

 

About CiMUS

The Singular Centre for Research in Molecular Medicine and Chronic Diseases (CiMUS) of the University of Santiago de Compostela is part of the network of research centres with a new organisational and operational model, which constitutes the fundamental element of the R&D strategy of the CAMPUS VIDA project (Campus of International Excellence, MEC-MICINN, 2009). The mission of CiMUS is to carry out basic research of proven quality, with the aim of achieving advances in the prevention, understanding and treatment of chronic disease. The centre has been awarded CIGUS recognition by the Xunta de Galicia, which accredits the quality and impact of its research. More information on the website https://cimus.usc.gal/ or follow us on social media @cimususc (Twitter, Instagram and LinkedIn).