Researchers at the Autonomous University of Madrid (UAM) have discovered that R-Ras1 and R-Ras2 proteins regulate the diversity of subpopulations of oligodendrocytes, the cells responsible for producing myelin in the central nervous system. This finding, published in Glia, could lay the foundations for new regenerative therapies for diseases such as multiple sclerosis.
A Spanish team, led by Dr. Beatriz Cubelos from the Universidad Autónoma de Madrid (UAM) and the Centro de Biología Molecular Severo Ochoa (CBM-CSIC-UAM), has identified that R-Ras1 and R-Ras2 proteins play a crucial role in the regulation of several subpopulations of oligodendrocytes, the cells responsible for producing myelin in the central nervous system.
The finding, published in the journal Glia, could open up new opportunities to develop regenerative therapies for neurodegenerative diseases such as multiple sclerosis and neuromyelitis optica.
Mature oligodendrocytes (MOLs) are essential for the rapid transmission of neuronal signals. Their dysfunction or loss is associated with demyelinating diseases, in which the ability to transmit nerve information is severely impaired. Although previous research has suggested that MOLs do not constitute a homogeneous population, until now it was not known how their subpopulations balance and differentiate under normal and pathological conditions.
Key proteins in the cellular diversity of oligodendrocytes.
Dr. Cubelos’ team explored the role of the GTPases R-Ras1 and R-Ras2 in the diversity of these myelin-producing oligodendrocytes. Their experiments revealed that, in mice lacking these proteins, a significant imbalance in oligodendrocyte subpopulations occurs, suggesting that R-Ras1 and R-Ras2 are essential for maintaining the heterogeneity and myelinating functionality of these cells.
"This discovery allows us to better understand the mechanisms that regulate oligodendrocyte diversity, an essential knowledge to design targeted therapies that can improve the quality of life of people with demyelinating diseases," highlights Cubelos.
The work also involved the participation of scientists from the University of Alcalá de Henares (UAH), the Carlos III National Center for Cardiovascular Research (CNIC), the Pablo de Olavide University (Seville), the Center for Biomedical Research Network on Neurodegenerative Diseases (CIBERNED) and the Spanish National Research Council (CSIC).
Bibliographic reference:
Alcover-Sánchez, B., Garcia-Martin, G., Paleo-García, V., Quintas, A., Dopazo, A., Gruart, A., Delgado-García, J. M., de la Villa, P., Wandosell, F. (2024). R-Ras1 and R-Ras2 regulate mature oligodendrocyte subpopulations. Glia. https://doi.org/10.1002/glia.24643
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