Scientists have discovered that Lin28 is a major regulator of axon regeneration and a promising therapeutic target for spinal cord injuries.
Scientists at the Lewis Katz School of Medicine Temple University (PA, USA) have demonstrated that the molecule Lin28 can fuel axon regeneration in mice with spinal cord injury or optic nerve injury. Currently there are no effective treatments for these types of injury. The study, published in Molecular Therapy in April, is the first to establish the regenerative ability of Lin28 upregulation.
Patients with spinal cord injuries have life-long losses in sensation and motor function due to irreparable damage to axons. Shuxin Li and colleagues at Temple University became interested in Lin28 as a therapeutic target due to its role in 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,” Li explained. To investigate further, the team used a neuron-specific Thy1 promotor to generate transgenic mice which overexpress Lin28 protein.
The mouse model revealed that upregulation of Lin28 stimulated long-distance axon regeneration leading to significant improvements in walking and sensory abilities. What is more, overexpression of Lin28, delivered post-injury with adeno-associated virus type 2 vector, also stimulated dramatic axon regeneration.
“We observed a lot of axon regrowth, which could be very significant clinically, since there currently are no regenerative treatments for spinal cord injury or optic nerve injury,” Li commented.
The team also demonstrated that upregulation of Lin28 enhances activity of the Akt signaling pathway in mature central nervous system neurons, indicating that Lin28 is critical for regulating growth capacity.
“Lin28 associates closely with other growth signaling molecules, and we suspect it uses multiple pathways to regulate cell growth,” Li explained. He hopes to further decipher the molecular details of the signaling pathway which could be packaged with Lin28 to aid axon regeneration.
However, the researchers’ immediate goal is to identify a safe and effective means of getting Lin28 to injured tissues in human patients. This requires developing a vector or carrier system which can be injected systemically and could hone in on injured axons.