Neurotrophins are crucial for the development, maintenance, and function of vertebrate nervous systems. They activate two main receptor classes: the Trk family of receptor tyrosine kinases and p75NTR, a member of the TNF receptor superfamily. These receptors trigger various signaling pathways, including those involving Ras, cdc-42/ras/rho G proteins, and cascades like MAP kinase, PI-3 kinase, and Jun kinase. During development, neurotrophins act as survival factors, ensuring the correct number of surviving neurons and regulating cell fate decisions, axon growth, and synaptic function. In the mature nervous system, they continue to control synaptic function and plasticity while modulating neuronal survival. Neurotrophins include NGF, BDNF, NT-3, and NT-4, all derived from a common ancestral gene. They are synthesized in various tissues, including sympathetic and sensory target organs, and are transported along axons to neuronal cell bodies. Other sources include macrophages in injured nerves and sensory neurons themselves, which can synthesize and release neurotrophins. Neurotrophins bind to Trk receptors, which are divided into TrkA, TrkB, and TrkC, each with distinct target neurons. p75NTR, a low-affinity receptor, also binds all neurotrophins and can either enhance or inhibit signaling depending on the context. Trk receptors mediate signaling through tyrosine kinase pathways, influencing survival, differentiation, axon growth, and synaptic function. The cytoplasmic domain of Trk receptors contains tyrosine residues that, when phosphorylated, activate downstream signaling cascades. p75NTR can also regulate signaling, sometimes promoting apoptosis or enhancing survival, depending on the context. The interaction between Trk and p75NTR is complex, with Trk signaling often counteracting p75NTR-mediated apoptosis, while both can influence NFκB activation, a key pathway for cell survival. Neurotrophins regulate the actin cytoskeleton through small G proteins like Cdc-42, Rac, and Rho, which control F-actin polymerization and turnover. Membrane trafficking and sorting also regulate Trk signaling, with internalization of Trk receptors being essential for efficient signaling. Adapter proteins like Shc, FRS-2, and Grb-2 play critical roles in linking Trk receptors to downstream signaling pathways. p75NTR can also activate signaling pathways, including NFκB and Jun kinase, which are involved in cell survival and apoptosis. The signaling pathways activated by neurotrophins are complex and involve multiple interactions, including those with PI-3 kinase, which is crucial for neuronal survival. The interplay between Trk and p75NTR receptors determines the overall outcome of neurotrophin signaling, with Trk receptors generally promoting survivalNeurotrophins are crucial for the development, maintenance, and function of vertebrate nervous systems. They activate two main receptor classes: the Trk family of receptor tyrosine kinases and p75NTR, a member of the TNF receptor superfamily. These receptors trigger various signaling pathways, including those involving Ras, cdc-42/ras/rho G proteins, and cascades like MAP kinase, PI-3 kinase, and Jun kinase. During development, neurotrophins act as survival factors, ensuring the correct number of surviving neurons and regulating cell fate decisions, axon growth, and synaptic function. In the mature nervous system, they continue to control synaptic function and plasticity while modulating neuronal survival. Neurotrophins include NGF, BDNF, NT-3, and NT-4, all derived from a common ancestral gene. They are synthesized in various tissues, including sympathetic and sensory target organs, and are transported along axons to neuronal cell bodies. Other sources include macrophages in injured nerves and sensory neurons themselves, which can synthesize and release neurotrophins. Neurotrophins bind to Trk receptors, which are divided into TrkA, TrkB, and TrkC, each with distinct target neurons. p75NTR, a low-affinity receptor, also binds all neurotrophins and can either enhance or inhibit signaling depending on the context. Trk receptors mediate signaling through tyrosine kinase pathways, influencing survival, differentiation, axon growth, and synaptic function. The cytoplasmic domain of Trk receptors contains tyrosine residues that, when phosphorylated, activate downstream signaling cascades. p75NTR can also regulate signaling, sometimes promoting apoptosis or enhancing survival, depending on the context. The interaction between Trk and p75NTR is complex, with Trk signaling often counteracting p75NTR-mediated apoptosis, while both can influence NFκB activation, a key pathway for cell survival. Neurotrophins regulate the actin cytoskeleton through small G proteins like Cdc-42, Rac, and Rho, which control F-actin polymerization and turnover. Membrane trafficking and sorting also regulate Trk signaling, with internalization of Trk receptors being essential for efficient signaling. Adapter proteins like Shc, FRS-2, and Grb-2 play critical roles in linking Trk receptors to downstream signaling pathways. p75NTR can also activate signaling pathways, including NFκB and Jun kinase, which are involved in cell survival and apoptosis. The signaling pathways activated by neurotrophins are complex and involve multiple interactions, including those with PI-3 kinase, which is crucial for neuronal survival. The interplay between Trk and p75NTR receptors determines the overall outcome of neurotrophin signaling, with Trk receptors generally promoting survival