Neurotrophin-3 (NT-3)
<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">Neurotrophin-3 (NT-3)</th>
</tr>
<tr> [@sofroniew2001]
<td class="label">Gene</td>
<td>[NTF3](/genes/ntf3)</td>
</tr>
<tr>
<td class="label">UniProt</td>
<td><a href="https://www.uniprot.org/uniprot/P20783" target="_blank">P20783</a></td>
</tr>
<tr>
<td class="label">PDB</td>
<td><a href="https://www.rcsb.org/structure/1B8M" target="_blank">1B8M</a></td>
</tr>
<tr>
<td class="label">Mol. Weight</td>
<td>13.6 kDa (precursor), 28.5 kDa (mature dimer)</td>
</tr>
<tr>
<td class="label">Localization</td>
<td>Secreted, extracellular</td>
</tr>
<tr>
<td class="label">Family</td>
<td>Neurotrophin family</td>
</tr>
<tr>
<td class="label">Receptors</td>
<td>[TrkC](/proteins/trkc) (primary), [p75NTR](/proteins/p75ntr)</td>
</tr>
<tr>
<td class="label">Diseases</td>
<td>[Alzheimer's Disease](/diseases/alzheimers), [Parkinson's Disease](/diseases/parkinsons-disease), [Huntington's Disease](/diseases/huntingtons)</td>
</tr>
</table>
Neurotrophin-3 (NT-3)
Introduction
Neurotrophin 3 (Nt 3) is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
Overview
...Neurotrophin-3 (NT-3)
<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">Neurotrophin-3 (NT-3)</th>
</tr>
<tr> [@sofroniew2001]
<td class="label">Gene</td>
<td>[NTF3](/genes/ntf3)</td>
</tr>
<tr>
<td class="label">UniProt</td>
<td><a href="https://www.uniprot.org/uniprot/P20783" target="_blank">P20783</a></td>
</tr>
<tr>
<td class="label">PDB</td>
<td><a href="https://www.rcsb.org/structure/1B8M" target="_blank">1B8M</a></td>
</tr>
<tr>
<td class="label">Mol. Weight</td>
<td>13.6 kDa (precursor), 28.5 kDa (mature dimer)</td>
</tr>
<tr>
<td class="label">Localization</td>
<td>Secreted, extracellular</td>
</tr>
<tr>
<td class="label">Family</td>
<td>Neurotrophin family</td>
</tr>
<tr>
<td class="label">Receptors</td>
<td>[TrkC](/proteins/trkc) (primary), [p75NTR](/proteins/p75ntr)</td>
</tr>
<tr>
<td class="label">Diseases</td>
<td>[Alzheimer's Disease](/diseases/alzheimers), [Parkinson's Disease](/diseases/parkinsons-disease), [Huntington's Disease](/diseases/huntingtons)</td>
</tr>
</table>
Neurotrophin-3 (NT-3)
Introduction
Neurotrophin 3 (Nt 3) is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
Overview
Neurotrophin-3 (NT-3) is a member of the neurotrophin family of growth factors that includes nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin-4/5 (NT-4). NT-3 plays crucial roles in the development, survival, and function of the nervous system, with particular importance for sensory [neurons](/entities/neurons), sympathetic neurons, and certain populations of central nervous system neurons.<sup>[1]</sup>
Biochemistry and Structure
NT-3 is synthesized as a precursor protein (pre-pro-NT-3) that undergoes proteolytic processing to generate the mature, biologically active form. Like other neurotrophins, NT-3 forms homodimers that are secreted and signal through specific receptor tyrosine kinases.<sup>[2]</sup>
The protein structure consists of:
- Signal peptide: Targets the protein for secretion
- Pro-domain: Involved in protein folding and trafficking
- Mature domain: Binds to TrkC receptors with high affinity
Normal Physiological Functions
Neuronal Development
During development, NT-3 supports the survival and differentiation of various neuronal populations, including:
- Dorsal root ganglion neurons
- Sympathetic ganglion neurons
- Certain cortical and hippocampal neurons
- Vestibular and auditory neurons<sup>[3]</sup>
Synaptic Plasticity
NT-3 modulates synaptic transmission and plasticity in the mature nervous system. It influences:
- [Long-term potentiation](/mechanisms/long-term-potentiation) (LTP) in hippocampal neurons
- Synaptic vesicle release
- Dendritic spine morphology<sup>[4]</sup>
Neuroprotection
NT-3 provides neuroprotective effects against various insults:
- Oxidative stress
- Excitotoxicity
- Ischemic injury
Role in Neurodegenerative Diseases
Alzheimer's Disease
In Alzheimer's disease, NT-3 levels are altered in affected brain regions. Studies show:
- Reduced NT-3 expression in the [hippocampus](/brain-regions/hippocampus) and [cortex](/brain-regions/cortex) of AD patients
- NT-3 can protect against [amyloid-beta](/proteins/amyloid-beta) toxicity
- NT-3 signaling may be impaired due to changes in TrkC expression<sup>[5]</sup>
Parkinson's Disease
NT-3 shows promise in Parkinson's disease research:
- Protects dopaminergic neurons from toxicity
- Promotes survival of ventral mesencephalic neurons
- May enhance graft survival in cell transplantation therapies<sup>[6]</sup>
Huntington's Disease
NT-3 is considered a therapeutic target in Huntington's disease:
- Mutant [huntingtin](/proteins/huntingtin) affects NT-3 signaling
- NT-3 delivery improves behavioral outcomes in animal models
- Supports striatal neuron survival<sup>[7]</sup>
Therapeutic Potential
NT-3 and its analogs have been investigated for:
- Gene therapy: AAV-mediated NT-3 delivery to the brain
- Small molecule agonists: TrkC-selective compounds
- Cell therapy: NT-3-secreting neural stem cells
- Peripheral neuropathy: NT-3 has been tested in clinical trials for chemotherapy-induced neuropathy
Key Publications
Maisonpierre PC, et al. (1990). Neurotrophin-3: a neurotrophic factor related to NGF and BDNF. Science 247(4949 Pt 1):1446-1451. [DOI:10.1126/science.247.4949.1446](https://doi.org/10.1126/science.247.4949.1446)
Robinson RC, et al. (1999). The structures of the neurotrophins and their receptors. Ann N Y Acad Sci 897:65-76. [DOI:10.1111/j.1749-6632.1999.tb07873.x](https://doi.org/10.1111/j.1749-6632.1999.tb07873.x)
Farinas I, et al. (1994). NT-3, like NGF, is a trophic factor for several neuronal populations in the developing chick central nervous system. J Neurosci 14(1):129-143.
Schinder AF, et al. (2000). The role of neurotrophins in synaptic development and plasticity. Curr Opin Neurobiol 10(3):400-408.
Naeem M, et al. (2022). Neurotrophin-3 and Alzheimer's disease: Molecular mechanisms and therapeutic strategies. Life Sci 298:120481.
Yoon SY, et al. (2020). Neurotrophin-3 protects dopaminergic neurons from oxidative stress. Mol Neurobiol 57(2):991-1003.
Xie Y, et al. (2020). Neurotrophin-3 ameliorates Huntington's disease through TrkC signaling. Neurobiol Dis 143:105006.See Also
- [NTF3 Gene](/genes/ntf3)
- [Brain-Derived Neurotrophic Factor (BDNF)](/proteins/bdnf)
- [Nerve Growth Factor (NGF)](/nerve-growth-factor-(ngf)))))))))))))
- [TrkC Receptor](/proteins/trkc)
- [Neurotrophin Signaling Pathway](/mechanisms/neurotrophin-signaling)
- [Neurotrophic Factors in Neurodegeneration](/neurotrophic-factors-in-neurodegeneration)
External Links
- [UniProt: P20783](https://www.uniprot.org/uniprot/P20783)
- [PDB: 1B8M](https://www.rcsb.org/structure/1B8M)
- [Human Protein Atlas: NTF3](https://www.proteinatlas.org/ENSG00000185652-NTF3)
Background
The study of Neurotrophin 3 (Nt 3) has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
References
[Maisonpierre PC, Belluscio L, Squinto S, et al, Neurotrophin-3: a neurotrophic factor related to NGF and BDNF (1990)](https://pubmed.ncbi.nlm.nih.gov/1688633/)
[Farinas I, Jones LR, Backus C, Wang XY, Reichardt LF, Severe sensory and sympathetic deficits in mice lacking neurotrophin-3 (1994)](https://pubmed.ncbi.nlm.nih.gov/7511219/)
[Lamballe F, Klein R, Barbacid M, TrkC, a receptor for neurotrophin-3 (1991)](https://pubmed.ncbi.nlm.nih.gov/1715884/)
[Binder DK, Routbort MJ, McNamara JO, Immunohistochemical evidence for seizure-induced activation of trkB receptors in the mossy fiber pathway of adult mouse hippocampus (1999)](https://pubmed.ncbi.nlm.nih.gov/10341261/)
[Sofroniew MV, Howe CL, Mobley WC, Nerve growth factor signaling, neuroprotection, and neural repair (2001)](https://pubmed.ncbi.nlm.nih.gov/11520933/)