title: Neu3 sialidase-mediated ganglioside conversion is necessary for axon regeneration and is blocked in CNS axons.
abstract: PNS axons have a high intrinsic regenerative ability, whereas most CNS axons show little regenerative response. We show that activation of Neu3 sialidase, also known as Neuraminidase-3, causing conversion of GD1a and GT1b to GM1 ganglioside, is an essential step in regeneration occurring in PNS (sensory) but not CNS (retinal) axons in adult rat. In PNS axons, axotomy activates Neu3 sialidase, increasing the ratio of GM1/GD1a and GM1/GT1b gangliosides immediately after injury in vitro and in vivo. No change in the GM1/GD1a ratio after axotomy was observed in retinal axons (in vitro and in vivo), despite the presence of Neu3 sialidase. Externally applied sialidase converted GD1a ganglioside to GM1 and rescued axon regeneration in CNS axons and in PNS axons after Neu3 sialidase blockade. Neu3 sialidase activation in DRGs is initiated by an influx of extracellular calcium, activating P38MAPK and then Neu3 sialidase. Ganglioside conversion by Neu3 sialidase further activates the ERK pathway. In CNS axons, P38MAPK and Neu3 sialidase were not activated by axotomy.
authors: John van Geest Centre for Brain Repair, University of Cambridge, Cambridge, CB2 0PY, United Kingdom, School of Medicine, University of St. Andrews, St. Andrews, KY16 9TF, United Kingdom, Membrane Biology and Axonal Repair Laboratory Hospital Nacional de Parapléjicos, E-45071 Toledo, Spain, and Centro de Biología Molecular Severo Ochoa, 28049, Madrid, Spain.
authors: Sunil
authors: S
authors: Kappagantula
authors: Melissa R
authors: MR
authors: Andrews
authors: Menghon
authors: M
authors: Cheah
authors: José
authors: J
authors: Abad-Rodriguez
authors: Carlos G
authors: CG
authors: Dotti
authors: James W
authors: JW
authors: Fawcett
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology*; D019771:Axotomy; D004789:Enzyme Activation / Q000502:physiology; D005732:Gangliosides / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D009416:Nerve Regeneration / Q000502:physiology*; D009439:Neuraminidase / Q000378:metabolism*; D034741:RNA, Small Interfering; D051381:Rats; D017207:Rats, Sprague-Dawley; D055351:Retinal Neurons / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D011984:Sensory Receptor Cells / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D014162:Transfection
chemical_list: D005732:Gangliosides; D034741:RNA, Small Interfering; D009439:Neuraminidase
keywords: Neu3 sialidase; axon regeneration; axotomy; gangliosides