Neurotrophins, crucial for central nervous system (CNS) functions, are synthesized as precursors (proneurotrophins) and cleaved to produce mature proteins that promote neuronal survival and synaptic plasticity by activating Trk receptors. Recent studies show that proneurotrophins, through interaction with p75 neurotrophin receptor (p75NTR), can have opposing effects to mature neurotrophins, highlighting a 'yin and yang' mechanism in neurotrophin action. Neurotrophins, including NGF, BDNF, NT3, and NT4, act via two receptor classes: p75NTR and Trk receptors. Proneurotrophins are secreted and can be cleaved by extracellular proteases like MMP7 and plasmin to form mature neurotrophins. This cleavage regulates neurotrophin action, with pro- and mature neurotrophins acting through different receptors to elicit opposing biological responses. The 'yin and yang' model of neurotrophin action suggests that the form of neurotrophin (pro- vs. mature) and the receptor class determine the cellular outcome. Proneurotrophins, acting via p75NTR, can induce apoptosis, while mature neurotrophins promote survival. This model has implications for synaptic plasticity, with mature BDNF promoting long-term potentiation (LTP) and proBDNF promoting long-term depression (LTD). The regulation of neurotrophin secretion and processing is complex, involving intracellular and extracellular cleavage, and is influenced by factors like tPA and plasmin. The pro-domain of neurotrophins plays a critical role in intracellular trafficking and secretion, with interactions with sortilin and CPE being essential for regulated secretion. The study highlights the importance of the pro-domain in neurotrophin function, with mutations affecting trafficking and secretion. The 'yin and yang' model extends to other cellular processes, including cell survival, synaptic plasticity, and structural modifications of synapses. ProBDNF, through p75NTR, promotes synaptic depression, while mature BDNF, via TrkB, promotes synaptic strengthening. These findings suggest that neurotrophins regulate synaptic plasticity through opposing mechanisms, with implications for understanding and treating neurological disorders. Future research will explore the role of pro- and mature neurotrophins in other aspects of neurotrophin function, such as neurogenesis and synapse formation.Neurotrophins, crucial for central nervous system (CNS) functions, are synthesized as precursors (proneurotrophins) and cleaved to produce mature proteins that promote neuronal survival and synaptic plasticity by activating Trk receptors. Recent studies show that proneurotrophins, through interaction with p75 neurotrophin receptor (p75NTR), can have opposing effects to mature neurotrophins, highlighting a 'yin and yang' mechanism in neurotrophin action. Neurotrophins, including NGF, BDNF, NT3, and NT4, act via two receptor classes: p75NTR and Trk receptors. Proneurotrophins are secreted and can be cleaved by extracellular proteases like MMP7 and plasmin to form mature neurotrophins. This cleavage regulates neurotrophin action, with pro- and mature neurotrophins acting through different receptors to elicit opposing biological responses. The 'yin and yang' model of neurotrophin action suggests that the form of neurotrophin (pro- vs. mature) and the receptor class determine the cellular outcome. Proneurotrophins, acting via p75NTR, can induce apoptosis, while mature neurotrophins promote survival. This model has implications for synaptic plasticity, with mature BDNF promoting long-term potentiation (LTP) and proBDNF promoting long-term depression (LTD). The regulation of neurotrophin secretion and processing is complex, involving intracellular and extracellular cleavage, and is influenced by factors like tPA and plasmin. The pro-domain of neurotrophins plays a critical role in intracellular trafficking and secretion, with interactions with sortilin and CPE being essential for regulated secretion. The study highlights the importance of the pro-domain in neurotrophin function, with mutations affecting trafficking and secretion. The 'yin and yang' model extends to other cellular processes, including cell survival, synaptic plasticity, and structural modifications of synapses. ProBDNF, through p75NTR, promotes synaptic depression, while mature BDNF, via TrkB, promotes synaptic strengthening. These findings suggest that neurotrophins regulate synaptic plasticity through opposing mechanisms, with implications for understanding and treating neurological disorders. Future research will explore the role of pro- and mature neurotrophins in other aspects of neurotrophin function, such as neurogenesis and synapse formation.