The objective of this project is to develop potential approaches to the therapy of brain and spinal cord injury. One approach is to limit the production or increase the degradation of chondroitin sulfate proteoglycans (CSPGs). We have demonstrated that the enzyme arylsulfatase B (ARSB), which cleaves the 4-sulfate group from chondroitin sulfate only at the non-reducing end, can dramatically increase neuronal growth on substrates of chondroitin sulfate. We have investigated the role of CSPGS in the injured optic nerve following optic nerve crush. We have demonstrated a significant upregulation of CSPGs in the moue optic nerve. We have also shown that ARSB can significantly improve the regeneration of axons in the mouse optic nerve following optic nerve crush. A manuscript describing these results has been published.

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Project End
Budget Start
Budget End
Support Year
8
Fiscal Year
2018
Total Cost
Indirect Cost
Name
U.S. National Heart Lung and Blood Inst
Department
Type
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Pearson, Craig S; Mencio, Caitlin P; Barber, Amanda C et al. (2018) Identification of a critical sulfation in chondroitin that inhibits axonal regeneration. Elife 7:
Janecke, Andreas R; Li, Ben; Boehm, Manfred et al. (2016) The phenotype of the musculocontractural type of Ehlers-Danlos syndrome due to CHST14 mutations. Am J Med Genet A 170A:103-15
Yi, Jae-Hyuk; Katagiri, Yasuhiro; Yu, Panpan et al. (2014) Receptor protein tyrosine phosphatase ? binds to neurons in the adult mouse brain. Exp Neurol 255:12-8
Geller, Herbert M (2013) Above the genome. Int J Dev Neurosci 31:351-2
Yi, Jae-Hyuk; Katagiri, Yasuhiro; Susarla, Bala et al. (2012) Alterations in sulfated chondroitin glycosaminoglycans following controlled cortical impact injury in mice. J Comp Neurol 520:3295-313