neurotrophin

Neurotrophins are a family of secreted growth factors that promote the survival, development, and function of neurons. The core members are nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and neurotrophin-4/5 (NT-4/5). They exert their effects primarily through Trk receptor tyrosine kinases—TrkA for NGF, TrkB for BDNF and NT-4/5, and TrkC for NT-3—alongside the pan-neurotrophin receptor p75NTR, which can modulate outcomes depending on context.

Neurotrophins are synthesized as prepropeptides and processed to mature ligands; pro-neurotrophins can be secreted and often signal via p75NTR to elicit distinct responses such as apoptosis. Mature neurotrophins activate Trk receptors, triggering intracellular signaling cascades including the PI3K/Akt pathway (promoting survival), the Ras/MAPK/ERK pathway (supporting differentiation and growth), and the PLCγ pathway (involved in calcium signaling and synaptic function).

Functionally, neurotrophins support the development of the nervous system and the maintenance of mature neurons, influence synaptic transmission and plasticity, and contribute to adult neurogenesis in regions such as the hippocampus. They play important roles in learning and memory and in responses to injury.

Clinical relevance: altered neurotrophin signaling is associated with neurodegenerative diseases, mood disorders, and cognitive disorders. Therapeutic approaches explore delivering NGF or BDNF to the CNS, using gene therapy or viral vectors, and developing Trk receptor agonists or mimetics, though delivery across the blood-brain barrier remains a challenge.