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>Neurotrophin & Neurotrophin Receptor
Neurotrophin & Neurotrophin Receptor
Neurotrophin & Neurotrophin Receptor Information
Neurotrophin & Neurotrophin Receptor Products
Neurotrophins & Neurotrophin Receptors
Neurotrophins are a family of growth factors that are capable of stimulating the survival, development and function of neurons. Neurotrophins act by preventing the associated neuron from initiating programmed cell death, and thus allowing the neurons to survive. Neurotrophins also help to stimulate and control neurogenesis, a process that new neurons develop from neural stem cells. The term "Neurotrophin" refers to four structurally related neurotrophic factors: nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and neurotrophin-4 (NT-4). Novel neurotrophin-1 (NNT1) is another neurotrophic factor, but it is structurally unrelated to NGF, BDNF, NT-3 and NT-4. Neurotrophins act through two classes of receptors: p75 and the Trk family of receptor tyrosine kinases (TrkA, TrkB and TrkC). Each neurotrophin has been shown to activate one or more of the three Trks. p75 neurotrophin receptor (p75NTR), a member of the tumour necrosis factor receptor superfamily, is also activated by each neurotrophin. Neurotrophins stimulate signaling pathways controlled through Ras, phosphatidyl inositol-3 (PI3)-kinase and phospholipase C-gamma1. Neurotrophins control the survival and development of neurons. Neurotrophins also play important roles in regulating axon growth, dendrite cell growth and pruning and the expression of proteins. Aberrant control of neurotrophins and their receptors lead to many diseases. For example, the neurotrophin receptor p75 is related to Alzheimer's disease.
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, 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). More...
Neurotrophin binding to neurons is comprised of 'high-affinity' and 'low-affinity' Neurotrophin receptor. The high attinity Neurotrophin receptor is Trk family which belongs to neurotrophic tyrosine kinase receptors. Trk family consists of TrkA, TrkB and TrkC. NGF binds to TrkA, BDNF and NT-4 bind to TrkB and NT-3 binds to TrkC. In addition NT-3 also binds to and activates TrkA and TrkB but it does so less efficiently. The low affinity Neurotrophin receptor is NGFR, also named p75 or p75 NTR, to which all neurotrophins bind. More...
Neurotrophin Pathway / Signaling
Trk family and P75NTR are the main receptors in Neurotrophin pathway / signaling. In general, Neurotrophin binds to these receptors and tiggers Neurotrophin pathway / signaling downstream. Neurotrophin binding to Trk receptors leads to their activation and to the recruitment of different proteins that associate with specific phosphotyrosine residues in the cytoplasmic domain of Trk receptors. These interactions trigger the activation of various signaling pathways, such as the Ras, Rap, PI3K, and PLCγpathways, which result in survival, neurite outgrowth, gene expression and synaptic plasticity. Binding of mature neurotrophins or pro-neurotrophins to p75NTR triggers the activation of different signaling pathways through different adaptors that result in diverse and at times opposite outcomes like survival, apoptosis, axonal growth, axonal collapse, and cell cycle arrest. Receptor tyrosine kinases are usually activated upon binding of their cognate ligands, but they can also be transactivated in response to G protein-coupled receptor (GPCR) signaling. More...
In the peripheral and central neurons, neurotrophins are important regulators for survival, differentiation, and maintenance of nerve cells. They are small proteins that secrete into the nervous system to help keep nerve cells alive. There are two distinct classes of glycosylated receptors that can bind to neurotrophins. These two proteins are p75 (NTR), which binds to all neurotrophins, and subtypes of Trk, which are only specific for each different neurotrophins. The signaling pathways activated by neurotrophins through Trk receptors result in many neuronal functions, such as cell survival, differentiation, dendritic arborization, synapse formation, plasticity, axonal growth, and axonal guidance. Functions ascribed to the p75NTR receptor are diverse, complex, and sometimes contradictory. p75NTR has been implicated in both promoting survival and inducing apoptosis, enhancing neurite outgrowth and facilitating growth-cone collapse, and mediating differentiation and enhancing proliferation. Moreover, p75NTR may also play a role in myelination. More...
Neurotrophin & Receptor Related Studies
- Pitts EV, et al. (2006) Neurotrophin and Trk-mediated signaling in the neuromuscular system. Int Anesthesiol Clin. 44(2):21-76.
- Chao MV, et al. (2006) Neurotrophin signalling in health and disease. Clin Sci (Lond). 110(2):167-73.
- Reichardt LF. (2006) Neurotrophin-regulated signalling pathways. Philos Trans R Soc Lond B Biol Sci. 361(1473):1545-64.
- Diarra A, et al. (2009) Signaling of the neurotrophin receptor p75 in relation to Alzheimer's disease. Biochem Biophys Res Commun. 390(3):352-6.