Neurotrophin



Neurotrophins, also called "neurotrophic factors", are a family of protein which induce the survival of neurons. They belong to a family of programmed cell death - thus allowing the neurons to survive. Neurotrophins also induce differentiation of progenitor cells, to form neurons.

The neurotrophin family includes neurotrophin-3 (NT-3), and neurotrophin-4 (NT-4).

Receptors

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. It is a member of the tumour necrosis super family.
  • The Trk family include TrkC, and will only bind with specific neurotrophins, but with a much higher affinity. The Trks mediate the functional signals of the neurotrophins.
  • 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.
  • Whilst the Trk receptors have a clearly defined trophic role, p75 receptors activate signalling pathways which can also result in apoptosis.

Nerve growth factor

Main article: Nerve growth factor

Nerve growth factor (NGF), the prototypical 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[citation needed].

Brain-derived neurotrophic factor

Main article: Brain-derived neurotrophic factor

Brain-derived neurotrophic factor (BDNF) is a 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 NGF and before neurotrophin-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, and the prostate.Neurotrophin self-production by an individual is described in "Keep Your Brain Alive" Workman Publishing 1999

Neurotrophin-1

Neurotrophin-1 (NT-1) is also known as "B cell-stimulating factor-3" (BSF-3) or "cardiotrophin-like cytokine factor 1" (CLCF1), and is a cytokine belonging to the interleukin-6 family. It is a secreted protein, found predominantly in lymph nodes and spleen, which contains 225 amino acids with a molecular mass of 22 kDa in its mature form. It is closely related to other proteins called cardiotrophin-1 and ciliary neurotrophic factor.

NNT-1/BSF-3 induces serum amyloid A, and in B cell hyperplasia. This cytokine is capable of B cell activation via gp130 receptor stimulation.[1]

Neurotrophin-3

Main article: Neurotrophin-3

Neurotrophin-3, or NT-3, is a NT-3 was the third neurotrophic factor to be characterized, after NGF and BDNF.

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 have loss of proprioceptive and subsets of mechanoreceptive sensory neurons. Interestingly, anti-depressant drugs produce behavioural changes mainly through gradual effect on BDNF and desensitisement of autoreceptors.

Neurotrophin-4

Main article: NT-4

Neurotrophin-4 (NT-4) like receptor tyrosine kinase. It is also known as NT4, NT5, NTF4, and NT-4/5.[2]

References

  1. ^ Senaldi et al., Novel neurotrophin-1/B cell-stimulating factor-3: a cytokine of the IL-6 family. Proc Natl Acad Sci U S A. 1999 September 28;96(20):11458-63
  2. ^ Entrez database entry for NT-4/5. NCBI. Retrieved on 2007-05-07.
  • Arévalo J, Wu S (2006). "Neurotrophin signaling: many exciting surprises!". Cell Mol Life Sci 63 (13): 1523-37. PMID 16699811.
  • Hempstead B (2006). "Dissecting the diverse actions of pro- and mature neurotrophins". Curr Alzheimer Res 3 (1): 19-24. PMID 16472198.
  • Allen S, Dawbarn D (2006). "Clinical relevance of the neurotrophins and their receptors". Clin Sci (Lond) 110 (2): 175-91. PMID 16411894.
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