Identification of a critical sulfation in chondroitin that inhibits axonal regeneration
Craig S Pearson, Caitlin P Mencio, Amanda C Barber, Keith R Martin, Herbert M Geller
eLife | ELIFE SCIENCES PUBLICATIONS LTD | Published : 2018
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 clini..View full abstract
Awarded by National Institutes of Health
Awarded by NATIONAL HEART, LUNG, AND BLOOD INSTITUTE
National Institutes of Health 1ZIAHL006135 Craig S Pearson Caitlin P Mencio Herbert M GellerCambridge Eye Trust Amanda C Barber Keith R MartinThe funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.