of growth of regenerating axons exposed to inhibitory proteins of CNS myelin, such as Nogo, MAG or OMgP. Without p75NTR, OMgP can activate RhoA and inhibit CNS axon regeneration. Coexpression of p75NTR and OMgP suppress RhoA activation. A complex of NgR1, p75NTR and LINGO1 can activate RhoA. p75NTR-mediated signaling pathways NF-kB activation NF-kB is a transcription factor that can be activated by p75NTR. Nerve growth factor (NGF) is a neurotrophin that promotes neuronal growth, and, in the absence of NGF, neurons die. Neuronal death in the absence of NGF can be prevented by NF-kB activation. Phosphorylated IκB kinase binds to and activates NF-kB before separating from NF-kB. After separation, IκB degrades and NF-kB continues to the nucleus to initiate pro-survival transcription. NF-kB also promotes neuronal survival in conjunction with NGF. NF-kB activity is activated by p75NTR, and is not activated via Trk receptors. NF-kB activity does not effect Brain-derived neurotrophic factor promotion of neuronal survival. RhoGDI and RhoA p75NTR serves as a regulator for actin assembly. Ras homolog family member A (RhoA) causes the actin cytoskeleton to become rigid which limits growth cone mobility and inhibits neuronal elongation in the developing nervous system. p75NTR without a ligand bound activates RhoA and limits actin assembly, but neurotrophin binding to p75NTR can inactivate RhoA and promote actin assembly. p75NTR associates with the Rho GDP dissociation inhibitor (RhoGDI), and RhoGDI associates with RhoA. Interactions with Nogo can strengthen the association between p75NTR and RhoGDI. Neurotrophin binding to p75NTR inhibits the association of RhoGDI and p75NTR, thereby suppressing RhoA release and promoting growth cone elongation (inhibiting RhoA actin suppression). JNK signaling pathway Neurotrophin binding to p75NTR activates the c-Jun N-terminal kinases (JNK) signaling pathway causing apoptosis of developing neurons. JNK, through a series of intermediates, activates p53 and p53 activates Bax which initiates apoptosis. TrkA can prevent p75NTR-mediated JNK pathway apoptosis. JNK-Bim-EL signaling pathway JNK can directly phosphorylate Bim-EL, a splicing isoform of Bcl-2 interacting mediator of cell death (Bim), which activates Bim-EL apoptotic activity. JNK activation is required for apoptosis but c-jun, a protein in the JNK signaling pathway, is not always required. Caspase-dependent signaling LNGFR also activates a caspase-dependent signaling pathway that promotes developmental axon pruning, and axon degeneration in neurodegenerative disease. In the apoptosis pathway, members of the TNF receptor superfamily assemble a death-inducing signaling complex (DISC) in which TRADD or FADD bind directly to the receptor's death domain, thereby allowing