Lin28 protein regulates CNS axon regeneration in adult mammalians


Shuxin Li, MD, PhD.
Associate Professor, Anatomy and Cell Biology
Associate Professor, Shriners Hospitals Pediatric Research Center

Lab Abstract:
Severed CNS axons fail to regenerate in adult mammals and there are no effective regenerative strategies to treat patients with CNS injuries. Several genes, including PTEN and Krüppel-like factors, regulate intrinsic growth capacity of mature neurons. However, none of these approaches were translated to clinics yet and thus there is a persistent need to identify better targets and improved delivery methods. Lin28, an RNA-binding protein, enhances translation of multiple genes including metabolic enzymes for increasing glycolysis and oxidative phosphorylation, and is essential for cell development and pluripotency in worms and mammals. Lin28 is a gatekeeper molecule to control switch between pluripotency and committed cells and its reactivation stimulates repair of several tissue systems, including hair, cartilage, bone, and mesenchyme. In this study, we reprogram mature CNS neurons with Lin28 activation to increase their growth capacity after CNS injuries. Especially, we evaluated the role of Lin28a in regulating regenerative capacity of different types of CNS neurons in adult mammals. Using neuron-specific Thy1 promoter, we generated transgenic mice that overexpress Lin28a protein in multiple neuronal populations, including multiple descending projection tracts and retinal ganglion cells. We demonstrate that upregulation of Lin28a in adult transgenic mice induces significant long distance regeneration of descending motor axons after spinal cord injury and optic fibres following optic nerve axotomy. Importantly, overexpression of Lin28a by post-injury treatment with AAV2 vector also stimulates dramatic regeneration of corticospinal tracts after spinal cord injury and optic axons after optic injury. Upregulation of Lin28a also enhances survival of retinal ganglion cells after injury and activity of Akt/mTOR signalling pathway in various CNS neurons. Therefore, Lin28a is critical for regulating growth capacity of CNS neurons and may become an important molecular target for treating for CNS injuries, including traumatic spinal cord and brain injury.

Shriners Hosp. Pediatric Res. Ctr., Temple Univ. Sch. of Med., Philadelphia, PA. Lin28 protein regulates CNS axon regeneration in adult mammalians. Program No. 115.07. 2018 Neuroscience Meeting Planner. San Diego, CA: Society for Neuroscience, 2018. Online.

Grant Support: NIH 1R01NS079432 and 1R01EY024575,  SHC-85100, SHC-86300-PHI, SHC-86200-PHI-16, SHC-85112-PHI-18

Also taking place in the Li Lab: 

Lab 2018 NIH Grant:  Acute Neural Injury and Epilepsy Study Section (ANIE) {R01-NS105961-01}  Develop a combinatorial therapy for spinal cord injury 

Temple Health Article:  Temple Scientists Identify Novel Target for Neuron Regeneration and Functional Recovery in Spinal Cord Injury

Technology Networks:  Protein Therapy Boosts Spinal Cord Regeneration in Mice

Molecular Therapy: Promoting axon regeneration in adult CNS by targeting liver kinase B1


This entry was posted in Chronic Spinal Cord Injury Research, Neuroscience Abstracts, Regenerative Medicine, spinal cord injury research, Stem Cell Research and tagged , , , . Bookmark the permalink.

1 Response to Lin28 protein regulates CNS axon regeneration in adult mammalians

  1. Mohammed Abdul Muneer says:

    Excellent work! Congratulations Dr. Li and team!

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