Neurotrophins and Cell Death

Early in development, the nervous system overproduces neurons and synapses. Throughout development, this initial surplus of cells is reduced and the connections between them refined via tightly controlled cell death. Cell death is regulated by a family of secreted proteins known as the neurotrophins. The four members of this family, nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin 3 (NT-3), and neurotrophin 4 (NT-4), have unique expression patterns and act through their receptors on distinct neuronal populations at different stages throughout development and in adulthood. In addition to controlling the balance between neuronal survival and cell death, neurotrophins regulate neuronal differentiation, connectivity and function, making them essential for proper nervous system development. Dysregulation of neurotrophins or their receptors at critical stages during development results in neurodevelopmental disorders that arise from perturbations in neuronal survival, proliferation, differentiation, synaptic function, connectivity, and plasticity.