They belong to a class of growth factors, secreted proteins that can signal particular cells to survive, differentiate, or grow.

[7] During the development of the vertebrate nervous system, many neurons become redundant (because they have died, failed to connect to target cells, etc.)

[8] Such cells control their degree of innervation (the number of axon connections) by the secretion of various specific neurotrophic factors that are essential for neuron survival.

One of these is nerve growth factor (NGF or beta-NGF), a vertebrate protein that stimulates division and differentiation of sympathetic and embryonic sensory neurons.

[11][12] In the peripheral and central neurons, neurotrophins are important regulators for survival, differentiation, and maintenance of nerve cells.

This movement of NGF from axon tip to soma is thought to be involved in the long-distance signaling of neurons.

In the brain, it is active in the hippocampus, cortex, cerebellum, and basal forebrain – areas vital to learning, memory, and higher thinking.

Mice born without the ability to make NT-3 have loss of proprioceptive and subsets of mechanoreceptive sensory neurons.

[citation needed] Neurotrophin-4 (NT-4) is a neurotrophic factor that signals predominantly through the TrkB receptor tyrosine kinase.

[17] It has been proposed that DHEA may have been the ancestral ligand of the Trk receptors early on in the evolution of the nervous system, eventually being superseded by the polypeptide neurotrophins.

[22] Neurotrophic survival signals in neurons are mediated by the high-affinity binding of neurotrophins to their respective Trk receptor.

[22] The PCD which occurs during brain development is responsible for the loss of a majority of neuroblasts and differentiating neurons.

[28][30] The expression of TrkA or TrkC receptors in the absence of neurotrophins can lead to apoptosis, but the mechanism is poorly understood.

[22] This is thought to be because it is differentially located in the cell membrane while TrkA and TrkC are co-localized with p75NTR in lipid rafts.

[24][32] However, in the CNS (where BDNF is mainly secreted in the spinal cord, substantia nigra, amygdala, hypothalamus, cerebellum, hippocampus and cortex) more factors determine cell fate, including neural activity and neurotransmitter input.

[24][32] Neurotrophins in the CNS have also been shown to play a more important role in neural cell differentiation and function rather than survival.

[22] These knockout experiments resulted in the loss of several neuron populations including the retina, cholinergic brainstem and the spinal cord.