Editors' ChoiceRegenerative Medicine

Two Proteins, One Stone

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Science Translational Medicine  11 Dec 2013:
Vol. 5, Issue 215, pp. 215ec203
DOI: 10.1126/scitranslmed.3008072

In the human body, the liver and spinal cord are at opposite ends of the regeneration scale: Liver regenerates; spinal cord does not. Thus, individuals with spinal cord injury suffer from serious paralysis. Now, Takeuchi et al. explore the role of chondroitin sulfate (CS) on axonal growth, finding that regulating one gene,CS N-acetylgalactosaminyltransferase-1 (T1), can inhibit CS activity and promote recovery from spinal cord injury.

Takeuchi et al. knocked out T1 in mice (T1KO) and then subjected them to bilateral contusion injury induced at the 10th thoracic vertebrae. These injured mice produced 25% less CS and recovered faster than did wild-type controls and control animals treated with chondroitinase ABC, an enzyme that degrades CS, as shown by an increase in functional (serotonin-positive) axons and reduced fibrosis and glial scar formation. Conversely, injured T1KO mice produced 20-fold more heparan sulfate (HS), which acts opposite of CS by strongly promoting axonal growth, than did controls. Coupled with the decrease in CS, such tremendous increase in HS likely contributed to the recovery of the injured T1KO animals. The mechanism behind this finding, however, remains to be elucidated. Once mechanism is known, these findings could be translated to an elegant gene therapy for spinal cord injury, in which silencing the expression of only one gene affects two proteins to promote axon growth and spinal cord regeneration.

Kosei Takeuchi et al., Chondroitin sulphate N-acetylgalactosaminyl-transferase-1 inhibits recovery from neural injury. Nat. Comm. 4, 2740 (2013). [Full Text]

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