VEGFA — Vascular Endothelial Growth Factor A

VEGFA — Vascular Endothelial Growth Factor A

Introduction

Pathway Diagram

```mermaid
flowchart TD
VEGFA["VEGFA<br/>(Vascular Endothelial<br/>Growth Factor A)"]

%% Upstream regulation
IDH1["IDH1<br/>(Isocitrate<br/>Dehydrogenase 1)"]

%% Key pathways
Angiogenesis["Angiogenesis<br/>and Vascular<br/>Repair"]
Neuroprotection["Neuroprotection<br/>and Neuronal<br/>Survival"]
BBB["Blood-Brain<br/>Barrier<br/>Integrity"]

%% Neuroinflammatory processes
Neuroinflammation["Neuroinflammation"]
Inflammation["Systemic<br/>Inflammation"]

%% Neurodegenerative diseases
ALS["Amyotrophic<br/>Lateral Sclerosis<br/>(ALS)"]
Alzheimer["Alzheimer's<br/>Disease"]
MS["Multiple<br/>Sclerosis"]
Neurodegeneration["Neurodegeneration"]

%% Downstream targets
MET["MET<br/>(Hepatocyte Growth<br/>Factor Receptor)"]
APOB["APOB<br/>(Apolipoprotein B)"]

%% Therapeutic outcomes
TherapeuticTarget["Therapeutic<br/>Target"]
Biomarker["Disease<br/>Biomarker"]

%% Connections
IDH1 -->|"regulates"| VEGFA
VEGFA -->|"promotes"| Angiogenesis
VEGFA -->|"enhances"| Neuroprotection
VEGFA -->|"maintains"| BBB

VEGFA -->|"modulates"| Neuroinflammation
VEGFA -->|"associated_with"| Inflammation

VEGFA -->|"inhibits"| ALS
VEGFA -->|"biomarker_for"| ALS
VEGFA -->|"therapeutic_target"| Alzheimer
VEGFA -->|"biomarker_for"| Alzheimer
VEGFA -->|"therapeutic_target"| MS
VEGFA -->|"biomarker_for"| Neurodegeneration

VEGFA -->|"targets"| MET

VEGFA — Vascular Endothelial Growth Factor A

Introduction

Pathway Diagram

Vegfa — 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.

<!-- Gene Infobox -->
<div class="infobox infobox-gene">
<div class="infobox-header">VEGFA</div>
<div class="infobox-content">
<table>
<tr><th>Full Name</th><td>Vascular Endothelial Growth Factor A</td></tr>
<tr><th>Synonyms</th><td>VEGF, VEGF-A, VPF</td></tr>
<tr><th>Chromosome</th><td>6p21.1</td></tr>
<tr><th>NCBI Gene ID</th><td>7422</td></tr>
<tr><th>OMIM</th><td>193240</td></tr>
<tr><th>Ensembl ID</th><td>ENSG00000112715</td></tr>
<tr><th>UniProt ID</th><td>P15692</td></tr>
<tr><th>Protein</th><td>[VEGFA Protein](/proteins/vegfa-protein)</td></tr>
<tr><th>Associated Diseases</th><td>Alzheimer's Disease, Parkinson's Disease, ALS, Vascular Cognitive Impairment, Stroke</td></tr>
</table>
</div>
</div>

Overview

VEGFA (Vascular Endothelial Growth Factor A), commonly known as VEGF, is a critical signaling protein that stimulates angiogenesis (formation of new blood vessels) and increases vascular permeability. While primarily studied for its role in cancer and cardiovascular diseases, VEGF also plays important roles in the central nervous system, including neurogenesis, neuronal survival, and neuroprotection. Dysregulated VEGF signaling contributes to the pathogenesis of neurodegenerative diseases through effects on the neurovascular unit, cerebral blood flow, and blood-brain barrier integrity.

Normal Function

VEGF exerts its effects by binding to receptor tyrosine kinases (VEGFR-1/Flt-1 and VEGFR-2/KDR/Flk-1) on endothelial cells and other cell types. In the brain, VEGF is expressed by [neurons](/entities/neurons), [astrocytes](/entities/astrocytes), and [microglia](/entities/microglia), and acts in both paracrine and autocrine fashions.

Key Functions in the CNS

VEGF Isoforms

The VEGFA gene produces multiple isoforms through alternative splicing:

• VEGF₁₂₁ (VEGF121): Freely diffusible
• VEGF₁₆₅ (VEGF165): Heparin-binding, predominant isoform
• VEGF₁₈₉ (VEGF189): Highly heparin-bound
• VEGF₂₀₆ (VEGF206): Rare, highly heparin-bound

Role in Neurodegenerative Diseases

Alzheimer's Disease

VEGF plays complex, multifaceted roles in AD:

• Amyloid angiopathy: VEGF interacts with [Aβ](/proteins/amyloid-beta) to influence cerebral amyloid angiopathy (CAA)
• Neurovascular dysfunction: Reduced VEGF signaling contributes to BBB breakdown
• Compensatory angiogenesis: Increased VEGF in early AD may represent compensatory response
• Therapeutic potential: VEGF gene therapy shows promise in animal models

Parkinson's Disease

VEGF involvement in PD includes:

• Dopaminergic neuron survival: VEGF protects SNpc neurons
• Vascular changes: PD associated with altered cerebral vasculature
• Neuroinflammation: VEGF modulates microglial responses
• Clinical trials: VEGF gene therapy in early-stage PD

Amyotrophic Lateral Sclerosis

• VEGF deficiency accelerates disease progression in SOD1 mice
• VEGF overexpression extends survival in ALS models
• Therapeutic potential via AAV-VEGF delivery

Stroke and Vascular Cognitive Impairment

• VEGF is acutely protective in ischemic stroke
• Promotes revascularization and neurogenesis post-stroke
• Dysregulated VEGF contributes to vascular dementia

Therapeutic Targeting

VEGF-Based Therapies

| Approach | Compound | Status | Indication |
|----------|----------|--------|------------|
| Gene therapy | AAV-VEGF | Phase II | PD, AD |
| Protein therapy | VEGF₁₂₁ | Preclinical | Stroke |
| Peptide agonists | VEGF-mimetic peptides | Preclinical | AD |
| Small molecules | VEGF receptor agonists | Preclinical | Various |

Anti-VEGF Therapies (for pathological angiogenesis)

| Drug | Mechanism | Approved Use |
|------|-----------|--------------|
| Bevacizumab | Anti-VEGF antibody | Cancer |
| Ranibizumab | Anti-VEGF Fab fragment | AMD |
| Aflibercept | VEGF trap | AMD |

Note: Anti-VEGF therapies may impair normal brain angiogenesis

Animal Models

• VEGF knockout: Embryonic lethal, neural development defects
• VEGF haploinsufficient: Reduced angiogenesis, increased sensitivity to ischemia
• Neuron-specific VEGF: Neuroprotection without systemic angiogenesis
• VEGF overexpression: Increased angiogenesis, improved cognition

See Also

• [Blood-Brain Barrier](/entities/blood-brain-barrier)
• [Neurovascular Unit](/mechanisms/neurovascular-unit)
• [Cerebral Hypoperfusion Pathway](/mechanisms/cerebral-hypoperfusion)
• [VEGFA Protein](/proteins/vegfa-protein)
• [VEGFR2 Protein](/proteins/vegfr2-protein)

External Links

• [NCBI Gene: VEGFA](https://www.ncbi.nlm.nih.gov/gene/7422)
• [UniProt: VEGFA](https://www.uniprot.org/uniprot/P15692)
• [Human Protein Atlas: VEGFA](https://www.proteinatlas.org/ENSG00000112715-VEGFA)
• [PubMed Search: VEGFA neurodegeneration](https://pubmed.ncbi.nlm.nih.gov/?term=VEGFA+Alzheimer+OR+VEGFA+Parkinson)

Background

The study of Vegfa — 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> Storkebaum E, et al. Nat Rev Neurosci. 2009;10(10):703-714. PMID: 19763104(https://pubmed.ncbi.nlm.nih.gov/19763104/)

<sup>[2]</sup> Zaccarini M, et al. J Exp Clin Cancer Res. 2020;39(1):255. PMID: 33239094(https://pubmed.ncbi.nlm.nih.gov/33239094/)

<sup>[3]</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>[4]</sup> Lange C, et al. Neurobiol Aging. 2016;45:33-47. PMID: 27453334(https://pubmed.ncbi.nlm.nih.gov/27453334/)

<sup>[5]</sup> Yasuda M, et al. J Neurosci. 2018;38(21):4902-4918. PMID: 29626182(https://pubmed.ncbi.nlm.nih.gov/29626182/)

Pathway Diagram

The following diagram shows the key molecular relationships involving VEGFA — Vascular Endothelial Growth Factor A discovered through SciDEX knowledge graph analysis: