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Publication : Chondroitin sulphate N-acetylgalactosaminyl-transferase-1 inhibits recovery from neural injury.

First Author  Takeuchi K Year  2013
Journal  Nat Commun Volume  4
Pages  2740 PubMed ID  24220492
Mgi Jnum  J:279610 Mgi Id  MGI:6211324
Doi  10.1038/ncomms3740 Citation  Takeuchi K, et al. (2013) Chondroitin sulphate N-acetylgalactosaminyl-transferase-1 inhibits recovery from neural injury. Nat Commun 4:2740
abstractText  Extracellular factors that inhibit axon growth and intrinsic factors that promote it affect neural regeneration. Therapies targeting any single gene have not yet simultaneously optimized both types of factors. Chondroitin sulphate (CS), a glycosaminoglycan, is the most abundant extracellular inhibitor of axon growth. Here we show that mice carrying a gene knockout for CS N-acetylgalactosaminyltransferase-1 (T1), a key enzyme in CS biosynthesis, recover more completely from spinal cord injury than wild-type mice and even chondroitinase ABC-treated mice. Notably, synthesis of heparan sulphate (HS), a glycosaminoglycan promoting axonal growth, is also upregulated in TI knockout mice because HS-synthesis enzymes are induced in the mutant neurons. Moreover, chondroitinase ABC treatment never induces HS upregulation. Taken together, our results indicate that regulation of a single gene, T1, mediates excellent recovery from spinal cord injury by optimizing counteracting effectors of axon regeneration--an extracellular inhibitor of CS and intrinsic promoters, namely, HS-synthesis enzymes.
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