Figure 8.

Time course of events associated with NGF deprivation-induced axon degeneration of sympathetic neurons. After NGF deprivation, prodegenerative transcription is upregulated. Axoplasmic calcium is increased and enriched in spheroids before catastrophic phase. Spheroid formation is regulated by p75NTR, Rho activity, and caspase activation. The calcium electrochemical gradient across the membrane is disrupted by spheroidal rupture, which may also lead to the release of intra-axonal prodegenerative molecules to extracellular space, acting as extrinsic factors to promote degeneration in a paracrine or autocrine manner. We speculate that p75NTR plays an important role in calcium dynamics during the latent phase, whereas DR6 can be activated by prodegenerative NDCM to mediate downstream catastrophic degeneration pathways (e.g., DLK/JNK, calpastatin, calpain).