Molecular Mechanisms of Central Nervous System Axonal Regeneration and Remyelination: A Review

International Journal of Molecular Sciences, 2020 · DOI: 10.3390/ijms21218116 · Published: October 30, 2020

Regenerative Medicine Neurology Genetics

Simple Explanation

Damage to the central nervous system (CNS) can lead to severe neurological dysfunction because neurons have a limited ability to regenerate after injury in adults. The pathogenic nature of the extracellular environment in CNS injury, such as myelin debris and glial scars, have inhibitory eﬀects on axon regeneration. Recent advances in high-throughput technologies have accelerated the identiﬁcation of novel molecular mechanisms as a therapeutic target that eﬀectively regulates axon growth, regeneration, and remyelination.

Study Duration

Not specified

Participants

Not specified

Evidence Level

Review

Key Findings

1
Preventing extrinsic inhibitory signals like chondroitin sulfate proteoglycans (CSPGs) and myelin-associated glycoprotein (MAG) has been one of the promising approaches to promote axon regeneration.
2
Lysophosphatidic acid receptor 1 (Lpar1) was downregulated, and phospholipid phosphatase-related 1 (Lppr1) as upregulated genes in sprouting neurons, both of which are modulators of lysophosphatidic acid (LPA) signaling.
3
Circulating transforming growth factor-β1 (TGF-β1) facilitates remyelination in the adult central nervous system.

Research Summary

This review focuses on the mechanisms that regulate CNS regeneration, highlighting the history, recent eﬀorts, and questions left unanswered in this ﬁeld. It has been widely accepted that both extrinsic factors derived from the external environment of damaged axons and poor intrinsic potential for the regeneration of adult CNS neurons limit axonal regeneration and sprouting. Recent advances in omics analysis and other high-content techniques have accelerated the understanding of the molecular mechanisms of axonal regeneration and remyelination, which is the ﬁrst step toward that goal.

Practical Implications

Therapeutic Targets

Identified molecular mechanisms can be targeted to promote axon growth, regeneration, and remyelination after CNS injury.

Drug Development

Small molecule screening has identified potential compounds, like cholesterol-lowering drugs, that promote axonal regeneration, providing therapeutic possibilities.

Clinical Applications

Understanding systemic factors such as FGF21 and TGF-β1 opens new avenues for therapeutic interventions targeting the whole-body environment to enhance CNS repair.

Study Limitations

1
The exact mechanisms by which reconstructed neural circuits restore motor and cognitive functions remain unclear.
2
Further investigation is needed to translate molecular and cellular findings into effective clinical therapies.
3
Current research is mainly limited to the brain and spinal cord, and more research is needed to find strategies to take into account the whole-body environment.

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