Trophic, Metabolic and Immune Checkpoints of Remyelination Failure in CNS Disease

Remyelination failure is increasingly recognised as the primary driver of progressive neurological disability in chronic central nervous system (CNS) disease. Despite the presence of oligodendrocyte precursor cells at lesion sites, remyelination stalls in conditions such as multiple sclerosis, leaving axons exposed and vulnerable to irreversible degeneration. Understanding why a regenerative capacity exists but fails to deliver is one of the most pressing questions in translational neuroscience.

This Research Topic focuses specifically on the trophic and metabolic signals that act as permissive or restrictive checkpoints for remyelination. We are concerned with what goes wrong in the diseased CNS microenvironment: where trophic support breaks down, how metabolic stress undermines oligodendrocyte survival, and how inflammatory and glial signals shift from pro-repair to inhibitory. The emphasis throughout is on failure modes and their therapeutic implications, not on baseline developmental or circuit-level myelination processes.
Central questions include: Which growth factor and trophic factor deficiencies are causally linked to remyelination arrest? How do metabolic constraints within CNS lesions prevent oligodendrocyte maturation? What microglial activation states promote or suppress repair, and can they be therapeutically redirected? How do cytokine and immune networks override or reinforce trophic signals at the lesion site?

We welcome original research articles, reviews, and perspectives addressing, but not limited to, the following themes:
o Metabolic regulation of oligodendrocyte survival and myelin maintenance in CNS disease
o Growth factor signalling as a trophic checkpoint for remyelination
o Trophic factor deficiencies in demyelinating disease: mechanisms and therapeutic implications
o Microglial activation states as regulators of CNS remyelination
o Immune-trophic crosstalk in myelin repair: from debris clearance to oligodendrocyte support
o Cytokine and growth factor networks governing remyelination failure in neurological disease
Contributions grounded in disease-relevant models, patient-derived data, or translational frameworks are particularly encouraged. This collection aims to map the trophic and metabolic landscape of the failing lesion environment and identify intervention points that could shift the balance from remyelination failure to repair.

Article types and fees

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Case Report
• Data Report
• Editorial
• FAIR² Data
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• ... View all formats

Articles that are accepted for publication by our external editors following rigorous peer review incur a publishing fee charged to Authors, institutions, or funders.

Article types

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Case Report
• Data Report
• Editorial
• FAIR² Data
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• Original Research
• Perspective
• Review
• Systematic Review
• Technology and Code

Keywords: Remyelination failure, trophic factors, oligodendrocyte, demyelinating disease, microglial activation, CNS repair, growth factor signalling, metabolic regulation

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.