Upregulating Lin28a Promotes Axon Regeneration in Adult Mice with Optic Nerve and Spinal Cord Injury

Molecular Therapy, 2020 · DOI: https://doi.org/10.1016/j.ymthe.2020.04.010 · Published: August 1, 2020

Regenerative Medicine Neurology Genetics

Simple Explanation

The study investigates Lin28a's role in promoting axon regeneration in adult mice after CNS injuries. The Lin28 gene is essential for cell development and pluripotency. The researchers used transgenic mice to overexpress Lin28a in multiple populations of projection neurons. Upregulation of Lin28a induces signiﬁcant long distance regeneration. Post-injury treatment with AAV2 vector to overexpress Lin28a stimulates dramatic regeneration of descending spinal tracts and optic nerve axons. Lin28a is critical for regulating growth capacity of multiple CNS neurons.

Study Duration

8 weeks

Participants

Adult C57BL/6 mice

Evidence Level

Not specified

Key Findings

1
Upregulation of Lin28a in transgenic mice induces significant long-distance regeneration of corticospinal axons and the optic nerve in adult mice.
2
Overexpression of Lin28a by post-injury treatment with AAV2 vector stimulates dramatic regeneration of descending spinal tracts and optic nerve axons after lesions.
3
Upregulation of Lin28a also enhances activity of the Akt signaling pathway in mature CNS neurons.

Research Summary

This study demonstrates the novel function of Lin28 in controlling regrowth of motor and sensory neurons in adult mammalian CNS. Upregulating Lin28a stimulated dramatic and long distance regeneration of injured CSTs and optic nerves in adult rodents and also significantly promoted survival of RGCs. Manipulating Lin28a activity represents a very attractive approach for regenerating various types of cells, including different populations of CNS neurons.

Practical Implications

Therapeutic Potential

Lin28a upregulation is a promising therapeutic approach for neurological disorders involving CNS axonal damage.

Combination Therapies

Combining Lin28a activation with other approaches, like suppressing scar-sourced inhibitors, could lead to synergistic effects.

Clinical Translation

The study's findings may translate into applications for humans, particularly those with brain/spinal cord injury, stroke, and glaucoma, by enhancing neuronal survival and regeneration.

Study Limitations

1
Signaling pathways by which Lin28 controls neuronal growth in adult CNS remain largely unknown.
2
Whether Lin28 regulates regrowth of mature CNS neurons by the let-7 pathway remains unknown.
3
It is interesting to study whether Lin28 controls regrowth of other types of neurons (e.g., CSTs) also by a presynaptic regulation.

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