Central nervous system demyelinating diseases: glial cells at the hub of pathology

Inflammatory demyelinating diseases (IDDs) are among the main causes of inflammatory and neurodegenerative injury of the central nervous system (CNS) in young adult patients. Of these, multiple sclerosis (MS) is the most frequent and studied, as it affects about a million people in the USA alone. The understanding of the mechanisms underlying their pathology has been advancing, although there are still no highly effective disease-modifying treatments for the progressive symptoms and disability in the late stages of disease. Among these mechanisms, the action of glial cells upon lesion and regeneration has become a prominent research topic, helped not only by the discovery of glia as targets of autoantibodies, but also by their role on CNS homeostasis and neuroinflammation. In the present article, we discuss the participation of glial cells in IDDs, as well as their association with demyelination and synaptic dysfunction throughout the course of the disease and in experimental models, with a focus on MS phenotypes. Further, we discuss the involvement of microglia and astrocytes in lesion formation and organization, remyelination, synaptic induction and pruning through different signaling pathways. We argue that evidence of the several glia-mediated mechanisms in the course of CNS demyelinating diseases supports glial cells as viable targets for therapy development.

Automated summary

Inflammatory demyelinating diseases (IDDs) are a major cause of central nervous system (CNS) inflammation and neurodegeneration in young adult patients, with multiple sclerosis (MS) being the most common and studied disease. The understanding of the pathology mechanisms underlying IDD has advanced, but there is still a lack of effective treatments for the progressive symptoms and disability in the late stages. Glial cells have been identified as key players in lesion formation, remyelination, and synaptic dysfunction, making them potential targets for therapy development. This article discusses the involvement of glial cells in IDD, particularly in MS phenotypes, highlighting the importance of exploring glial-mediated mechanisms for future treatment strategies.