Identification of a critical sulfation in chondroitin that inhibits axonal regeneration

ELife
Craig S PearsonHerbert M Geller

Abstract

The failure of mammalian CNS neurons to regenerate their axons derives from a combination of intrinsic deficits and extrinsic factors. Following injury, chondroitin sulfate proteoglycans (CSPGs) within the glial scar inhibit axonal regeneration, an action mediated by the sulfated glycosaminoglycan (GAG) chains of CSPGs, especially those with 4-sulfated (4S) sugars. Arylsulfatase B (ARSB) selectively cleaves 4S groups from the non-reducing ends of GAG chains without disrupting other, growth-permissive motifs. We demonstrate that ARSB is effective in reducing the inhibitory actions of CSPGs both in in vitro models of the glial scar and after optic nerve crush (ONC) in adult mice. ARSB is clinically approved for replacement therapy in patients with mucopolysaccharidosis VI and therefore represents an attractive candidate for translation to the human CNS.

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Citations

Dec 7, 2019·Current Opinion in Neurology·Kimberly K GokoffskiPhillip Lam
Jul 3, 2020·Glycobiology·Haruna NagaseYasuhiro Katagiri
Sep 17, 2020·Annual Review of Vision Science·Philip R WilliamsZhigang He
Oct 8, 2018·Journal of Molecular Neuroscience : MN·Harshini Chakravarthy, Vasudharani Devanathan
Aug 28, 2020·Frontiers in Cellular Neuroscience·Rowan K HusseinHerbert M Geller
Feb 17, 2019·International Journal of Molecular Sciences·Francesco BorrielloGianni Marone
Aug 30, 2019·Nature Communications·Elizabeth J Bradbury, Emily R Burnside
Jan 12, 2021·Frontiers in Cell and Developmental Biology·Wenshuang WangFuchuan Li
Nov 11, 2019·Experimental Eye Research·Craig S PearsonHerbert M Geller
Aug 21, 2021·Cellular & Molecular Immunology·Joshua D CrapserKim N Green

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Methods Mentioned

BETA
Fluorescence

Software Mentioned

Zeiss
GraphPad
ImageJ
GraphPad Prism

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