Neurotrophin family consists of a family of proteins that implicated in several different functions in the nervous system, including survival, proliferation, differentiation, myelination, apoptosis, axonal growth, and synaptic plasticity. All of Neurotrophin family proteins belong to a class of growth factors, secreted proteins that are capable of signaling particular cells to survive, differentiate or grow. Growth factors such as neurotrophin family that promote the survival of neurons are known as neurotrophic factors. Neurotrophic factors are secreted by target tissue and act by preventing the associated neuron from initiating programmed cell death - thus allowing the neurons to survive.
The history of neurotrophin started 50 years ago when Levi-Montalcini, Cohen and Hamburger discovered nerve growth factor (NGF), the prototypical neurotrophin, as a factor requires for axonal growth from explants. 30 years later, other neurotrophin family proteins, brain-derived neurotrophin factor (BDNF), neurotrophin-3 (NT-3) and neurotrophin-4 (NT-4) were identified. From now on, the term Neurotrophin family is generally reserved for four structurally related factors: nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and neurotrophin-4 (NT-4).
Nerve growth factor (NGF) ,the prototypical growth factor of Neurotrophin family, is a protein secreted by a neuron's target cell. NGF is responsible for the survival and maintenance of the phenotype of specific subsets of peripheral neurones and basal forebrain cholinergic nuclei during development and maturation. This member of neurotrophin family binds to and activates its high affinity Neurotrophin family receptor TrkA on the neuron, and is internalized into the responsive neuron. The NGF / TrkA complex is subsequently trafficked back to the neuron's cell body. This movement of NGF from axon tip to soma is thought to be involved in the long-distance signaling of neurons. NGF also exerts a modulatory role on sensory, nociceptive nerve physiology during adulthood that appears to correlate with hyperalgesic phenomena occurring in tissue inflammation. Other NGF-responsive cells are now recognized as belonging to the haemopoietic–immune system and to populations in the brain involved in neuroendocrine functions. The concentration of NGF is elevated in a number of inflammatory and autoimmune states in conjunction with an increased accumulation of mast cells.
BDNF is another member of Neurotrophin family. BDNF is highly expressed in hippocampus, amygdala, cerebral cortex and cerebellum. It also can be detected in heart, lung, skeletal muscle, testis, prostate and placenta. BDNF is induced by cortical neurons which is necessary for survival of striatal neurons in the brain. BDNF has emerged a major regulator of synaptic transmission and plasticity at adult synapses in many regions of the CNS. This unique role within the neurotrophin family fits with the widespread distribution of BDNF and the co-localization of BDNF and its receptor, TrkB, at glutamate synapses. The versatility of BDNF is emphasized by its contribution to a range of adaptive neuronal responses including long-term potentiation (LTP), long-term depression (LTD), certain forms of short-term synaptic plasticity, as well as homeostatic regulation of intrinsic neuronal excitability.
NT-3 was the third member of Neurotrophin family to be characterized, after nerve growth factor (NGF) and BDNF (Brain-derived Neurotrophic Factor). NT-3 has activity on certain neurons of the peripheral and central nervous system. This protein is closely related to both nerve growth factor and brain-derived neurotrophic factor. NT-3 may be involved in the maintenance of the adult nervous system, and may affect development of neurons in the embryo when it is expressed in human placenta. NTF3-deficient mice display severe movement defects of the limbs. The mature peptide of this protein is identical in all mammals examined including human, pig, rat and mouse. NT-3 binds three receptors on the surface of cells which are capable of responding to this growth factor which are TrkC, TrkB and LNGFR.
NT-4 is a fourth neurotrophin family member which shares all of the features found in the mammalian neurotrophins. NT-4 is a neurotrophic factor that signals predominantly through the TrkB receptor tyrosine kinase.