Novel Molecular and Cellular Targets Driving Axon Regeneration After Spinal Cord Injury

Spinal cord injury (SCI) leads to devastating and often irreversible loss of sensory and motor function due to the limited regenerative capacity of the adult central nervous system. Axon regeneration, the ability of injured neurons to re-extend functional projections, is a critical prerequisite for restoring connectivity and neurological recovery. Despite decades of research, the molecular and cellular mechanisms that govern axon regeneration remain only partially understood. This Research Topic aims to highlight emerging molecular and cellular targets that drive axon regeneration following spinal cord injury. By integrating discoveries from transcriptomic profiling, genetic manipulation, and advanced imaging, this collection seeks to uncover new regulatory pathways and therapeutic strategies that promote axonal growth and synaptic reconnection after injury.

Axon regeneration is influenced by a complex interplay between intrinsic neuronal programs and extrinsic inhibitory environments. Recent advances in single-cell and spatial transcriptomics, multi-omics profiling, and functional genetic screening have revealed novel regulators, such as transcription factors, epigenetic modulators, and metabolic pathways, that may unlock the regenerative potential of injured neurons. At the same time, the microenvironment of the injured spinal cord, including glial cells, immune responses, and extracellular matrix components, plays a pivotal role in either constraining or supporting axon regeneration. Targeting these cellular interactions and signaling cascades provides new opportunities for enhancing regeneration and circuit repair.

Topics of interest include, but are not limited to:
- Intrinsic molecular regulators of axon regeneration.
- Cell-extrinsic modulation by astrocytes, microglia, and oligodendrocyte lineage cells.
- Neuron–glia and immune interactions shaping the regenerative microenvironment.
- Single-cell and spatial omics profiling of regenerative and non-regenerative neurons.
- Transcription factor-based neuronal reprogramming and gene therapy strategies.
- Bioengineered models and in vivo systems for studying circuit repair and regeneration.
- Translational applications and emerging molecular targets for functional recovery after SCI.

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
• Conceptual Analysis
• Data Report
• Editorial
• FAIR² Data
• FAIR² DATA Direct Submission
• General Commentary
• Hypothesis and Theory
• ... 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
• Conceptual Analysis
• Data Report
• Editorial
• FAIR² Data
• FAIR² DATA Direct Submission
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• Original Research
• Perspective
• Registered Report
• Review
• Study Protocol
• Systematic Review
• Technology and Code

Keywords: axon regeneration, spinal cord injury, molecular targets, neuronal reprogramming, glia interactions

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.