Neurotrophin-4 (NT-4)

Neurotrophin-4 (NT-4)

<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">Neurotrophin-4 (NT-4)</th>
</tr>
<tr> [@fryer1997]
<td class="label">Gene</td>
<td>[NTF4](/genes/ntf4)</td>
</tr>
<tr>
<td class="label">UniProt</td>
<td><a href="https://www.uniprot.org/uniprot/P34130" target="_blank">P34130</a></td>
</tr>
<tr>
<td class="label">PDB</td>
<td><a href="https://www.rcsb.org/structure/1B9E" target="_blank">1B9E</a></td>
</tr>
<tr>
<td class="label">Mol. Weight</td>
<td>13.9 kDa (precursor), 28.2 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>[TrkB](/proteins/trkb) (primary), [TrkC](/proteins/trkc) (lower affinity), [p75NTR](/proteins/p75ntr)</td>
</tr>
<tr>
<td class="label">Diseases</td>
<td>[Alzheimer's Disease](/diseases/alzheimers), [Parkinson's Disease](/diseases/parkinsons-disease), [ALS](/diseases/als)</td>
</tr>
</table>

Neurotrophin-4 (NT-4)

Introduction

Neurotrophin 4 (Nt 4) 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-4 (NT-4)

<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">Neurotrophin-4 (NT-4)</th>
</tr>
<tr> [@fryer1997]
<td class="label">Gene</td>
<td>[NTF4](/genes/ntf4)</td>
</tr>
<tr>
<td class="label">UniProt</td>
<td><a href="https://www.uniprot.org/uniprot/P34130" target="_blank">P34130</a></td>
</tr>
<tr>
<td class="label">PDB</td>
<td><a href="https://www.rcsb.org/structure/1B9E" target="_blank">1B9E</a></td>
</tr>
<tr>
<td class="label">Mol. Weight</td>
<td>13.9 kDa (precursor), 28.2 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>[TrkB](/proteins/trkb) (primary), [TrkC](/proteins/trkc) (lower affinity), [p75NTR](/proteins/p75ntr)</td>
</tr>
<tr>
<td class="label">Diseases</td>
<td>[Alzheimer's Disease](/diseases/alzheimers), [Parkinson's Disease](/diseases/parkinsons-disease), [ALS](/diseases/als)</td>
</tr>
</table>

Neurotrophin-4 (NT-4)

Introduction

Neurotrophin 4 (Nt 4) 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-4 (NT-4), also known as neurotrophin-4/5 (NT-4/5), is a member of the neurotrophin family that signals primarily through the TrkB receptor. While discovered later than NGF, BDNF, and NT-3, NT-4 has emerged as an important neurotrophic factor with unique physiological roles and therapeutic potential in neurodegenerative diseases.^[1]

Biochemistry and Structure

NT-4 shares structural homology with other neurotrophins but exhibits distinct receptor binding profiles:

• Precursor form: Contains signal peptide and pro-domain
• Mature form: Forms homodimers that bind to Trk receptors
• Receptor specificity: High affinity for TrkB, lower affinity for TrkC

Normal Physiological Functions

Motor Neuron Development

NT-4 is particularly important for:

• Survival of spinal cord motor [neurons](/entities/neurons)
• Neuromuscular junction formation
• Muscle fiber innervation^[2]

Sensory Neuron Support

NT-4 supports various sensory neuron populations:

• Cutaneous sensory neurons
• Vestibular neurons
• Photoreceptors

Synaptic Function

In the mature nervous system, NT-4:

• Modulates synaptic plasticity
• Regulates dendritic branching
• Influences [long-term potentiation](/mechanisms/long-term-potentiation)^[3]

Role in Neurodegenerative Diseases

Alzheimer's Disease

NT-4 shows altered expression in AD:

• Reduced hippocampal NT-4 levels correlate with cognitive decline
• NT-4 protects against [amyloid-beta](/proteins/amyloid-beta)-induced neuronal death
• TrkB signaling deficits may contribute to synaptic loss^[4]

Parkinson's Disease

Therapeutic potential in PD includes:

• Protection of dopaminergic neurons
• Support of nigrostriatal pathway integrity
• Enhancement of graft survival in transplantation^[5]

ALS

NT-4 may benefit motor neuron disease:

• Supports motor neuron survival
• Promotes neuromuscular junction stability
• May slow disease progression in models^[6]

Therapeutic Development

NT-4-based therapies are being explored for:

• Protein delivery: Recombinant NT-4 administration
• Gene therapy: AAV-NT-4 vectors
• Small molecule TrkB agonists
• Cell-based delivery: NT-4-secreting stem cells

Key Publications

Ip NY, et al. (1992). Mammalian neurotrophin-4: structure, chromosomal localization, tissue distribution, and receptor specificity. Proc Natl Acad Sci U S A 89(7):3060-3064.

Henderson CE, et al. (1993). Neurotrophin-4 is a target-derived trophic factor for motor neurons in vivo. Nature 364(6435):337-339.

Park H, Poo MM. (2013). Neurotrophin regulation of neural circuit development and function. Nat Rev Neurosci 14(1):7-23.

Allen SJ, et al. (2013). Neurotrophin-based therapies for Alzheimer's disease. Mol Ther 21(5):1066-1078.

Sortwell CE, et al. (2000). Neurotrophic factor-expressing ventral mesencephalic grafts improve forelimb use in a Parkinson model. Exp Neurol 163(2):440-452.

Nishio T, et al. (2008). Neurotrophin-4/5 enhances motoneuron survival in wobbler mice. J Neurosci Res 86(4):848-858.

See Also

• [NTF4 Gene](/genes/ntf4)
• [Brain-Derived Neurotrophic Factor (BDNF)](/proteins/bdnf)
• [TrkB Receptor](/proteins/trkb)
• [Neurotrophin Signaling Pathway](/mechanisms/neurotrophin-signaling)
• [Motor Neuron Diseases](/diseases/motor-neuron-diseases)

External Links

• [UniProt: P34130](https://www.uniprot.org/uniprot/P34130)
• [PDB: 1B9E](https://www.rcsb.org/structure/1B9E)
• [Human Protein Atlas: NTF4](https://www.proteinatlas.org/ENSG00000100244-NTF4)

Background

The study of Neurotrophin 4 (Nt 4) 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

[Ip NY, Stitt TN, Tapley P, et al, Similarities and differences in the way neurotrophins interact with the Trk receptors in neuronal and nonneuronal cells (1993)](https://pubmed.ncbi.nlm.nih.gov/8094964/)

[Klein R, Lamballe F, Barbacid M, The trkB tyrosine protein kinase encodes a receptor for neurotrophin-4 (1992)](https://pubmed.ncbi.nlm.nih.gov/1316766/)

[Berkemeier LR, Winslow JW, Kaplan DR, et al, Neurotrophin-5: a novel neurotrophic factor that activates trk and trkB (1991)](https://pubmed.ncbi.nlm.nih.gov/1681829/)

[Minichiello L, Klein R, TrkB and TrkC signaling in the maintenance and function of midbrain dopaminergic neurons (1996)](https://pubmed.ncbi.nlm.nih.gov/8946289/)

[Fryer RH, Kaplan DR, Kromer LF, Truncated trkB receptors on neurons and astrocytes (1997)](https://pubmed.ncbi.nlm.nih.gov/9417825/)