Diagram of proposed signaling cascade regulating Neu3 sialidase activity. Membrane rupture after axotomy leads to increased influx of eCa²⁺ into injured axons. Whereas in adult DRGs this results in either direct activation of Neu3 sialidase or an increased phosphorylation of P38MAPK resulting in increased Neu3 sialidase activation, this process is absent in adult retinal axons. Furthermore, ERK is activated downstream of Neu3 sialidase, which in turn further activates Neu3 sialidase through a positive feedback loop, a step attenuated in retinal axons, resulting in a two step block for successful Neu3 sialidase activity mediated regeneration.