Molecular mechanisms of the suppression of axon regeneration by KLF transcription factors

Neural Regeneration Research, 2014 · DOI: 10.4103/1673-5374.139454 · Published: August 1, 2014

Regenerative Medicine Neurology Genetics

Simple Explanation

Neurons in the central nervous system (CNS) often fail to regenerate axons after injury, which impacts neurodegenerative conditions. Understanding why is crucial. Embryonic neurons can regenerate axons, but adult neurons cannot, partly due to inhibitory molecules from glial cells like astrocytes and oligodendrocytes. KLF transcription factors, particularly KLF4 and KLF9, play a role in limiting axon regeneration ability in CNS neurons.

Study Duration

Not specified

Participants

Animal models

Evidence Level

Review article

Key Findings

1
KLF4 expression significantly decreased neurite outgrowth in hippocampal and cortical neurons, and RGCs.
2
KLF4 knockout during early development increased neurite growth from RGCs in vitro, and increased axon regeneration in vivo after optic nerve injury.
3
KLF9 also demonstrated a dramatic 250-fold increase in expression after birth, and overexpression of KLF9 resulted in a significant decrease in neurite outgrowth in vitro.

Research Summary

KLFs regulate intrinsic axon growth ability in central nervous system (CNS) neurons including retinal ganglion cells, and hippocampal and cortical neurons. Characterizing the molecular mechanisms of the KLF family in the nervous system, including binding partners and gene targets, may improve understanding of how KLFs regulate neurite growth and axon regeneration. Kinases such as those in the MAPK family, which are activated by extracellular signals such as neurotrophic factors, act on developmentally regulated transcription factors such as KLFs, which has important implications for understanding regenerative failure.

Practical Implications

Therapeutic Target Identification

Understanding KLF regulation may provide novel therapeutic targets for promoting axon regeneration after CNS injury or in neurodegenerative diseases.

Drug Development

Developing drugs that modulate KLF activity or their downstream targets could enhance axon growth and functional recovery.

Personalized Medicine

Identifying specific KLF-related pathways that are dysregulated in individual patients could allow for personalized treatment strategies.

Study Limitations

1
The precise downstream gene targets and binding partners of KLF9 in RGCs remain to be fully elucidated.
2
The kinases responsible for KLF6 phosphorylation have not yet been identified.
3
Characterizing the phosphorylation and phospho-regulation of other KLF family members within the CNS is an important goal for future study.

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