Lipin1 depletion coordinates neuronal signaling pathways to promote motor and sensory axon regeneration after spinal cord injury

PNAS, 2024 · DOI: https://doi.org/10.1073/pnas.2404395121 · Published: September 18, 2024

Spinal Cord Injury Regenerative Medicine Neurology

Simple Explanation

Traumatic injuries to the central nervous system (CNS) in mammals often lead to permanent functional impairments because the CNS has limited regeneration capacity. Here, we revealed that lipin1 modulates axon regeneration capacity by influencing cell signaling pathways critical for axon regeneration. Deleting lipin1 facilitates robust regrowth of multiple CNS axons following injury. This finding suggests a potential strategy for repairing the damaged neural network after spinal cord injury, offering hope for future clinical applications.

Study Duration

Not specified

Participants

WT, mTORf/f, Rptorf/f, and Tsc1f/f mice

Evidence Level

Not specified

Key Findings

1
Lipin1 orchestrates mechanistic target of rapamycin (mTOR) and STAT3 signaling pathways to determine axon regeneration.
2
Lipin1 KD enhances corticospinal tract (CST) sprouting after unilateral pyramidotomy and promotes CST regeneration following complete spinal cord injury (SCI).
3
Lipin1 KD enhances sensory axon regeneration after SCI.

Research Summary

In this study, we showed that lipin1 orchestrates mechanistic target of rapamycin (mTOR) and STAT3 signaling pathways to determine axon regeneration. Overall, our research reveals that lipin1 functions as a central regulator to coordinate mTOR and STAT3 signaling pathways in the CNS neurons and highlights the potential of lipin1 as a promising therapeutic target for promoting the regeneration of motor and sensory axons after SCI. These findings establish lipin1 as an important modulator of axon regeneration across diverse cell types.

Practical Implications

Therapeutic Target

Lipin1 is a potential therapeutic target for promoting regeneration of motor and sensory axons after SCI.

Clinical Translation

Inhibiting lipin1 in adulthood enhances CST sprouting, implying strong potential for clinical translation.

Functional Connections

Axon guidance factors may be necessary for other regenerated axons to establish functional connections.

Study Limitations

1
Whether the regenerated axons reform neural networks and restore function remains to be investigated.
2
Axon guidance factors may also be necessary for other regenerated axons to establish functional connections.
3
It is important to consider that axon guidance factors may also be necessary for other regenerated axons to establish functional connections.

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