VEGFA Protein - Vascular Endothelial Growth Factor A
Introduction
Pathway Diagram
Mermaid diagram (expand to render)
Vegfa Protein Vascular Endothelial Growth Factor A is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
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<div class="infobox-header">VEGFA Protein</div>
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<table>
<tr><th>Protein Name</th><td>Vascular Endothelial Growth Factor A</td></tr>
<tr><th>Gene</th><td>[VEGFA](/proteins/vegfa-protein)</td></tr>
<tr><th>UniProt ID</th><td>P15692</td></tr>
<tr><th>PDB ID</th><td>1VPF, 1M2I, 4KKS</td></tr>
<tr><th>Molecular Weight</th><td>19-24 kDa (depending on isoform)</td></tr>
<tr><th>Subcellular Localization</th><td>Secreted, extracellular</td></tr>
<tr><th>Protein Family</th><td>PDGF/VEGF family</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/als" style="color:#ef9a9a">ALS</a>, <a href="/wiki/ami" style="color:#ef9a9a">AMI</a>, <a href="/wiki/aging" style="color:#ef9a9a">Aging</a></td>
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<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">600 edges</a></td>
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Overview
VEGFA (Vascular Endothelial Growth Factor A) is a key signaling protein that stimulates angiogenesis, increases vascular permeability, and exerts neuroprotective effects. Originally characterized for its role in vascular development and tumor angiogenesis, VEGFA is now recognized as an important regulator of neuronal survival, neurogenesis, and synaptic plasticity in the central nervous system.
Structure
VEGFA is produced in multiple isoforms through alternative splicing:
| Isoform | Amino Acids | Properties |
|---------|-------------|------------|
| VEGF₁₂₁ | 121 | Freely diffusible |
| VEGF₁₆₅ | 165 | Heparin-binding, predominant |
| VEGF₁₈₉ | 189 | Highly cell-associated |
| VEGF₂₀₆ | 206 | Rare, cell-associated |
Structural Features
- Signal peptide: Secretory pathway targeting
- PDGF/VEGF domain: Receptor binding
- Heparin-binding domain: Present in longer isoforms
- Receptor-binding sites: VEGFR-1 and VEGFR-2 binding interfaces
Normal Function
Receptor Signaling
VEGFA signals through two main receptor tyrosine kinases:
VEGFR-2 (KDR/Flk-1): Primary signaling receptor
- Mediates angiogenesis
- Promotes endothelial cell survival
- Increases vascular permeability
VEGFR-1 (Flt-1): Decoy receptor
- Regulates VEGF activity
- Important in developmental angiogenesis
CNS Functions
- Angiogenesis: New blood vessel formation
- Neuroprotection: Direct anti-apoptotic effects on [neurons](/entities/neurons)
- Neurogenesis: Promotes neural progenitor cell proliferation
- Synaptic plasticity: Modulates excitatory neurotransmission
- Blood-brain barrier maintenance: Regulates endothelial tight junctions
Role in Neurodegeneration
Alzheimer's Disease
- VEGF interacts with amyloid pathology
- Neurovascular dysfunction in AD
- Potential for VEGF-based therapies
- Clinical trials of VEGF gene therapy
Parkinson's Disease
- Protects dopaminergic neurons
- Improves cerebral blood flow
- AAV-VEGF in clinical trials for PD
ALS
- VEGF deficiency accelerates disease
- Gene therapy approaches show promise
- Motor neuron survival effects
Stroke
- Acute neuroprotection
- Promotes post-ischemic angiogenesis
- Therapeutic window for VEGF delivery
Therapeutic Targeting
VEGF-Based Therapies
| Approach | Indication | Status |
|----------|------------|--------|
| AAV-VEGF gene therapy | PD, AD | Phase II |
| VEGF protein delivery | Stroke | Preclinical |
| VEGF receptor agonists | AD | Discovery |
VEGF Inhibitors (for pathological angiogenesis)
| Drug | Target | Approved Use |
|------|--------|--------------|
| Bevacizumab | VEGF | Cancer |
| Ranibizumab | VEGF | AMD |
| Aflibercept | VEGF | AMD |
See Also
- [VEGFA Gene](/proteins/vegfa-protein)
- [VEGFR2 Protein](/proteins/vegfr2-protein)
- [Blood-Brain Barrier](/entities/blood-brain-barrier)
- [Neurovascular Unit](/mechanisms/neurovascular-unit)
External Links
- [UniProt: VEGFA](https://www.uniprot.org/uniprot/P15692)
- [PDB: VEGF structures](https://www.rcsb.org/structure/1VPF)
- [Human Protein Atlas: VEGFA](https://www.proteinatlas.org/ENSG00000112715-VEGFA)
- [PubMed Search: VEGF neurodegeneration](https://pubmed.ncbi.nlm.nih.gov/?term=VEGF+neurodegeneration)
Background
The study of Vegfa Protein Vascular Endothelial Growth Factor A 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
<sup>[1]</sup> Ferrara N, et al. Nat Med. 2003;9(6):669-676. PMID: 12778165(https://pubmed.ncbi.nlm.nih.gov/12778165/)
<sup>[2]</sup> Storkebaum E, et al. Nat Rev Neurosci. 2009;10(10):703-714. PMID: 19763104(https://pubmed.ncbi.nlm.nih.gov/19763104/)
<sup>[3]</sup> Lange C, et al. Neurobiol Aging. 2016;45:33-47. PMID: 27453334(https://pubmed.ncbi.nlm.nih.gov/27453334/)
<sup>[4]</sup> Ruiz de Almodovar C, et al. J Cereb Blood Flow Metab. 2009;29(9):1543-1554. PMID: 19503051(https://pubmed.ncbi.nlm.nih.gov/19503051/)
<sup>[5]</sup> Zaccarini M, et al. J Exp Clin Cancer Res. 2020;39(1):255. PMID: 33239094(https://pubmed.ncbi.nlm.nih.gov/33239094/)