Researchers here show that the gene Lin28 regulates axon regrowth. In mice, raised levels of Lin28 produce greater regeneration of nerve injuries. Past research has investigated Lin28 from the standpoint of producing a more general improvement in regenerative capacity. It improves mitochondrial function, thus providing additional energy for cellular growth and replication. Researchers here employ a viral vector to deliver Lin28 to mice, which is a first step on the long road towards clinical applications. Practical therapies remain years in the future, however.
“Our findings show that Lin28 is a major regulator of axon regeneration and a promising therapeutic target for central nervous system injuries. We became interested in Lin28 as a target for neuron regeneration because it acts as a gatekeeper of stem cell activity. It controls the switch that maintains stem cells or allows them to differentiate and potentially contribute to activities such as axon regeneration.”
To explore the effects of Lin28 on axon regrowth, researchers developed a mouse model in which animals expressed extra Lin28 in some of their tissues. When full-grown, the animals were divided into groups that sustained spinal cord injury or injury to the optic nerve tracts that connect to the retina in the eye. Another set of adult mice, with normal Lin28 expression and similar injuries, were given injections of a viral vector for Lin28 to examine the molecule’s direct effects on tissue repair.
Extra Lin28 stimulated long-distance axon regeneration in all instances, though the most dramatic effects were observed following post-injury injection of Lin28. In mice with spinal cord injury, Lin28 injection resulted in the growth of axons to more than three millimeters beyond the area of axon damage, while in animals with optic nerve injury, axons regrew the entire length of the optic nerve tract. Evaluation of walking and sensory abilities after Lin28 treatment revealed significant improvements in coordination and sensation.