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Neurotrophins (or neurotrophic factors)are a family of molecules that encourage survival of nervous tissue. Neurotrophic factors are secreted by cells in a neuron's target field, and act by prohibiting the neuron from apoptosis. In this way, target neurons are not removed.

Neurotrophic factors are a family of proteins that are responsible for the growth and survival of developing neurons and the maintenance of mature neurons. Recent research has proven that neurotrophic factors promote the initial growth and development of neurons in the central nervous system and peripheral nervous system and that they are capable of regrowing damaged neurons in test tubes and animal models [1]. Neurotrophic factors are often released by the target tissue in order to guide the growth of developing axons. Most neurotrophic factors belong to one of three families: (1) neurotrophins, (2) glial cell-line derived neurotrophic factor family ligands (GFLs), and (3) neuropoietic cytokines [1]. Each family has its own distinct signaling family though the cellular responses elicited often do overlap [1].

The neurotrophin family include the growth factors Nerve Growth Factor (NGF), Brain-derived neurotrophic factor (BDNF), neurotrophin 3 (NT-3), and neurotrophin 4 (NT-4). There are two classes of receptors, p75 and the "Trk" family of Tyrosine kinases receptors. p75 is a low affinity neurotrophin receptor, to which all neurotrophins bind. The Trk family include TrkA, TrkB, and TrkC, and will only bind with specific neurotrophins, but with a much higher affinity. The Trks mediate the functional signals of the neurotrophins.

Currently, neurotrophic factors are being intensely studied for use in bioartificial nerve conduits because they are necessary in vivo for directing axon growth and regeneration. In studies, neurotrophic factors are normally used in conjunction with other techniques such as biological and physical cues created by the addition of cells and specific topographies. The neurotrophic factors may or may not be immobilized to the scaffold structure, though immobilization is preferred because it allows for the creation of permanent, controllable gradients. In some cases, such as neural drug delivery systems, they are loosely immobilized such that they can be selectively released at specified times and in specified amounts.

Nerve Growth Factor, NGFEdit

Nerve growth factor (NGF), the prototypical growth factor, is a protein secreted by a neuron's target. NGF is critical for the survival and maintenance of sympathetic and sensory neurons. NGF is released from the target cells, binds to and activates its high affinity receptor (TrkA), and is internalized into the responsive neuron. The NGF/TrkA complex is subsequently trafficked back to the cell body. This movement of NGF from axon tip to soma is thought to be involved in the long-distance signaling of neurons.

Brain-derived Neurotrophic Factor, BDNFEdit

Brain-derived neurotrophic factor (BDNF) is a neurotrophic factor found originally in the brain, but also found in the periphery. More specifically, it is a protein which has activity on certain neurons of the central nervous system and the peripheral nervous system; it helps to support the survival of existing neurons, and encourage the growth and differentiation of new neurons and synapses through axonal and dendritic sprouting. In the brain, it is active in the hippocampus, cortex, cerebellum, and basal forebrain—areas vital to learning, memory, and higher thinking. BDNF was the second neurotrophic factor to be characterized, after nerve growth factor (NGF) and before neurotrophin three (NT-3).

Although the vast majority of neurons in the mammalian brain are formed prenatally, parts of the adult brain retain the ability to grow new neurons from neural stem cells; a process known as neurogenesis. Neurotrophins are chemicals that help to stimulate and control neurogenesis, BDNF being one of the most active. Mice born without the ability to make BDNF suffer developmental defects in the brain and sensory nervous system, and usually die soon after birth, suggesting that BDNF plays an important role in normal neural development.

Despite its name, BDNF is actually found in a range of tissue and cell types, not just the brain. Expression can be seen in the retina, the CNS, motor neurons, the kidneys, the prostate and post-katiemorgan circuit.

Neurotrophin-3, NT-3Edit

Neurotrophin-3, or NT-3 is a neurotrophic factor, in the NGF (Nerve Growth Factor)-family of neurotrophins. It is a protein growth factor which has activity on certain neurons of the peripheral and central nervous system; it helps to support the survival and differentiation of existing neurons, and encourages the growth and differentiation of new neurons and synapses. NT-3 was the third neurotrophic factor to be characterized, after nerve growth factor (NGF) and BDNF (Brain Derived Neurotrohic Factor).

Although the vast majority of neurons in the mammalian brain are formed prenatally, parts of the adult brain retain the ability to grow new neurons from neural stem cells; a process known as neurogenesis. Neurotrophins are chemicals that help to stimulate and control neurogenesis. NT-3 is unique in the number of neurons it can potentially stimulate, given its ability to activate two of the receptor tyrosine kinase neurotrophin receptors (TrkC and TrkB - see below). Mice born without the ability to make NT-3 have loss of proprioceptive and subsets of mechanoreceptive sensory neurons.

Neurotrophin-4, NT-4Edit

NT-4, like (BDNF) is a neurotrophic factor that signals predominantly through the TrkB receptor tyrosine kinase.

ReferencesEdit

  • Deister, C. and C.E. Schmidt, Optimizing neurotrophic factor combinations for neurite outgrowth. Journal of Neural Engineering, 2006. 3: p. 172-179.

[1] "Neurotrophin signaling: many exciting surprises!", Cell Mol Life Sci. 2006 May 15; [Epub ahead of print]

[2] "Dissecting the diverse actions of pro- and mature neurotrophins", Curr Alzheimer Res. 2006 Feb;3(1):19-24.

[3] "Clinical relevance of the neurotrophins and their receptors", Clin Sci (Lond). 2006 Feb;110(2):175-91.

External linksEdit

  • DevBio.com - 'Neurotrophin Receptors: The neurotrophin family consists of four members: nerve growth factor (NGF), brain derived neurotrophic factor (BDNF), neurotrophin 3 (NT-3), and neurotrophin 4 (NT-4)' (April 4, 2003)
  • Dr.Koop.com - 'New Clues to Neurological Diseases Discovered: Findings could lead to new treatments, two studies suggest', Steven Reinberg, HealthDay (July 5, 2006)
  • Helsinki.fi - 'Neurotrophic factors'


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