Smoldering Inflammation in Multiple Sclerosis: Microenvironment, Metabolism, and Therapeutic Strategies

Multiple sclerosis (MS) is a chronic inflammatory and degenerative disease of the central nervous system (CNS) affecting nearly three million individuals worldwide. The complex interplay between glial, neural, and immune cells contributes to MS pathology and offers potential targets for therapeutic intervention. Recent studies have focused on the concept of 'smoldering inflammation,' which refers to the chronic, non-relapsing, and immune-mediated mechanism of disease progression. This inflammation is likely shaped and sustained by local factors in the CNS, such as cytokines, pH value, lactate levels, and nutrient availability. However, current treatments for MS do not sufficiently target this process, and there is a growing interest in understanding the role of environmental and lifestyle factors in altering immune cell metabolism and potentially contributing to smoldering pathology in the CNS.

This Research Topic aims to advance our understanding of the local inflammatory microenvironment in smoldering inflammation and its interaction with the metabolism of tissue-resident immune cells, as well as the potential role of environmental and lifestyle factors in MS progression. Additionally, the topic seeks to explore novel therapeutic targets and strategies, including the potential of targeting neuron-oligodendrocyte potassium shuttling at the nodes of Ranvier as a neuroprotective strategy and the role of astrocyte-specific therapies in limiting MS progression.

To gather further insights into the complex interplay between inflammation, metabolism, and neurodegeneration in MS, we welcome articles addressing, but not limited to, the following themes:

- The role of local factors in shaping and sustaining smoldering inflammation in the CNS

- The impact of environmental and lifestyle factors on immune cell metabolism and MS pathology

- Novel therapeutic targets and strategies for preventing smoldering inflammation and progressive neurodegenerative damage in MS

- The potential of targeting neuron-oligodendrocyte potassium shuttling as a neuroprotective strategy in MS

- The role of astrocyte-specific therapies in limiting MS progression and their potential as novel therapeutic approaches

- The role of infections in temporally worsening pre-existing symptoms

Keywords: MS, multiple sclerosis, smouldering inflammation, cytokines, potassium shuttling, nodes of Ranvier, astrocytes

Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.