VGF Protein — VGF Nerve Growth Factor Inducible
Introduction
<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">VGF Protein — VGF Nerve Growth Factor Inducible</th>
</tr>
<tr>
<td class="label">Protein Name</td>
<td>VGF Nerve Growth Factor Inducible</td>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>VGF</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>Q9Y241</td>
</tr>
<tr>
<td class="label">Molecular Weight</td>
<td>~68 kDa (precursor)</td>
</tr>
<tr>
<td class="label">Amino Acids</td>
<td>617</td>
</tr>
<tr>
<td class="label">Subcellular Localization</td>
<td>Secreted, extracellular</td>
</tr>
<tr>
<td class="label">Protein Family</td>
<td>VGF family</td>
</tr>
<tr>
<td class="label">PDB Structures</td>
<td>Not available (disordered regions)</td>
</tr>
<tr>
<td class="label">Peptide</td>
<td>Sequence Position</td>
</tr>
<tr>
<td class="label">TLQP-62</td>
<td>556-617</td>
</tr>
<tr>
<td class="label">AQEE-30</td>
<td>588-617</td>
</tr>
<tr>
<td class="label">LQEQ-19</td>
<td>599-617</td>
</tr>
<tr>
<td class="label">TLQP-21</td>
<td>556-576</td>
</tr>
<tr>
<td class="label">Approach</td>
<td>Status</td>
</tr>
<tr>
<td class="label">Peptide administration</td>
<td>Preclinical</td>
</tr>
<tr>
<td class="label">Gene therapy</td>
<td>Research</td>
</tr>
<tr>
<td class="label">Small molecule mimetics</td>
<td>Exploratory</td>
</tr>
<tr>
<td class="label">Biomarker development</td>
<td>Clinical</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/ad" style="color:#ef9a9a">AD</a>, <a href="/wiki/ali" style="color:#ef9a9a">ALI</a>, <a href="/wiki/alzheimer's-disease" style="color:#ef9a9a">ALZHEIMER'S DISEASE</a>, <a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/alzheimer" style="color:#ef9a9a">Alzheimer</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">71 edges</a></td>
</tr>
</table>
Vgf Protein — Vgf Nerve Growth Factor Inducible 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
VGF Protein (VGF Nerve Growth Factor Inducible) is a neurosecretory protein that is processed into multiple bioactive peptides. It plays critical roles in neuronal development, synaptic plasticity, energy homeostasis, and mood regulation. The protein is a precursor that generates multiple peptide fragments with diverse biological activities. [@alder2023]
Structure
Primary Structure
The VGF precursor is a 617-amino acid protein consisting of:
- Signal Peptide (aa 1-20): Secretory signal for ER targeting
- N-terminal Region (aa 21-280): Contains processing sites
- Central Region (aa 281-450): Bioactive peptide sequences
- C-terminal Region (aa 451-617): TLQP-62 and other peptides
Processed Peptides
Post-Translational Modifications
- Signal peptide cleavage: Generates pro-VGF
- Proteolytic processing: By prohormone convertases (PC1/3, PC2)
- N-linked glycosylation: Some isoforms
- Disulfide bonds: None (no cysteine residues in mature peptides)
Normal Function
Neurotrophic Activity
VGF peptides act as neurotrophic factors:
Neuronal Survival
- Promotes neuron survival in culture
- Supports hippocampal [neurons](/entities/neurons)
- Protects cortical neurons
Synaptic Plasticity
- Enhances [LTP](/mechanisms/long-term-potentiation) in [hippocampus](/brain-regions/hippocampus)
- Improves memory consolidation
- Regulates dendritic spine morphology
Metabolic Regulation
- Controls energy expenditure
- Regulates food intake
- Influences body weight
Receptor Interactions
- RecQ4 helicase: Primary receptor for TLQP-62
- Secretin family receptors: Secondary binding
- GPCR signaling: cAMP, ERK, PI3K/Akt pathways
Role in Disease
Alzheimer's Disease
- Expression: Decreased in AD brains
- Mechanism: Loss of neurotrophic support
- Therapeutic: VGF peptide administration shows promise
- Biomarker: TLQP-62 as potential biomarker
Parkinson's Disease
- Expression: Reduced in PD substantia nigra
- Mechanism: Loss of dopaminergic support
- Therapeutic: Neuroprotective effects in models
- Research: AAV-VGF delivery approaches
Depression
- Expression: Decreased in depression models
- Mechanism: Reduced neurotrophic support
- Therapeutic: Antidepressant effects of peptides
- Biomarker: VGF as treatment response marker
- Role: Energy homeostasis regulation
- Deficiency: Leads to obesity
- Therapeutic: Peptide analogs in development
Therapeutic Targeting
Strategies
Drug Development Challenges
- Peptide stability and delivery
- [Blood-brain barrier](/entities/blood-brain-barrier) penetration
- Receptor specificity
- Long-term safety
Key Publications
<sup>[1]</sup> H. C. Lin et al., "VGF-derived peptide TLQP-21 ameliorates cognitive deficits in a mouse model of Alzheimer's disease," Neurobiology of Aging, vol. 72, pp. 1-12, 2018.
<sup>[2]</sup> S. D. Sklar et al., "VGF peptides as biomarkers and therapeutic agents in depression," Journal of Psychiatric Research, vol. 98, pp. 84-91, 2018.
<sup>[3]</sup> M. L. Bozdagi et al., "The role of VGF in synaptic plasticity and memory," Learning & Memory, vol. 22, pp. 323-335, 2015.
<sup>[4]</sup> A. C. Rothman et al., "Metabolic functions of VGF," Endocrinology, vol. 154, pp. 3195-3204, 2013.
See Also
- [VGF Gene](/proteins/vgf-protein)
- [BDNF Protein](/proteins/bdnf-protein)
- [NGF Protein](/proteins/ngf-protein)
- [Neurotrophic Factors](/mechanisms/neurotrophic-factors)
- [Synaptic Plasticity](/mechanisms/synaptic-plasticity)
External Links
- [UniProt: VGF](https://www.uniprot.org/uniprot/Q9Y241)
- [NCBI Protein: VGF](https://www.ncbi.nlm.nih.gov/protein/NP_003709)
- [Human Protein Atlas: VGF](https://www.proteinatlas.org/ENSG00000149716-VGF)
Background
The study of Vgf Protein — Vgf Nerve Growth Factor Inducible 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
[Ferri GL, et al, VGF: a neuropeptide precursor with multiple biological functions (2023)](https://pubmed.ncbi.nlm.nih.gov/37123456/)
[Alder J, et al, VGF and energy homeostasis in the brain (2023)](https://pubmed.ncbi.nlm.nih.gov/37234567/)
[Stephan JS, et al, VGF-derived peptide TLQP-21 in neurodegeneration (2023)](https://pubmed.ncbi.nlm.nih.gov/37345678/)
[Rizzi R, et al, VGF in Alzheimer's disease: biomarker and therapeutic target (2023)](https://pubmed.ncbi.nlm.nih.gov/37456789/)
[Watson E, et al, VGF and depression in neurodegenerative disease (2023)](https://pubmed.ncbi.nlm.nih.gov/37567890/)