Retrograde Signaling in Axonal Regeneration

Neuronal regeneration in the peripheral nervous system requires mobilization of intrinsic neurite outgrowth mechanisms. This process depends on retrograde signaling between lesion site and soma to provide accurate and timely information on the nature and extent of axonal damage, and to elicit an appropriate cell body response. An early phase of electrophysiological signaling is followed by an ensemble of motor-driven signals, some of which are dependent on local protein translation in the axon and formation of an importins-coordinated retrograde complex. In addition to eliciting the cell body response, computational analyses suggest that this biphasic mechanism may provide information on the distance of the leson site from the neuronal cell body. Encouraging recent data suggest that it may be possible to apply this emerging understanding of retrograde signaling mechanisms to activate intrinsic regeneration mechanisms also in growth-refractory central neurons.