GDNF — Glial Cell Line-Derived Neurotrophic Factor

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GDNF — Glial Cell Line-Derived Neurotrophic Factor

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GDNF — Glial Cell Line-Derived Neurotrophic Factor

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">GDNF — Glial Cell Line-Derived Neurotrophic Factor</th>
</tr>
<tr>
<td class="label">Approach</td>
<td>Status</td>
</tr>
<tr>
<td class="label">AAV-GDNF gene therapy</td>
<td>Clinical trials</td>
</tr>
<tr>
<td class="label">GDNF protein infusion</td>
<td>Discontinued</td>
</tr>
<tr>
<td class="label">GFRα1 agonists</td>
<td>Preclinical</td>
</tr>
<tr>
<td class="label">Cell therapy</td>
<td>Preclinical</td>
</tr>
<tr>
<td class="label">Region</td>
<td>Expression Level</td>
</tr>
<tr>
<td class="label">Substantia nigra</td>
<td>High</td>
</tr>
<tr>
<td class="label">Striatum</td>
<td>Medium-High</td>
</tr>
<tr>
<td class="label">Hippocampus</td>
<td>Medium</td>
</tr>
<tr>
<td class="label">Cortex</td>
<td>Low-Medium</td>
</tr>
<tr>
<td class="label">Cerebellum</td>
<td>Low</td>
</tr>
</table>

Pathway Diagram

...

GDNF — Glial Cell Line-Derived Neurotrophic Factor

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">GDNF — Glial Cell Line-Derived Neurotrophic Factor</th>
</tr>
<tr>
<td class="label">Approach</td>
<td>Status</td>
</tr>
<tr>
<td class="label">AAV-GDNF gene therapy</td>
<td>Clinical trials</td>
</tr>
<tr>
<td class="label">GDNF protein infusion</td>
<td>Discontinued</td>
</tr>
<tr>
<td class="label">GFRα1 agonists</td>
<td>Preclinical</td>
</tr>
<tr>
<td class="label">Cell therapy</td>
<td>Preclinical</td>
</tr>
<tr>
<td class="label">Region</td>
<td>Expression Level</td>
</tr>
<tr>
<td class="label">Substantia nigra</td>
<td>High</td>
</tr>
<tr>
<td class="label">Striatum</td>
<td>Medium-High</td>
</tr>
<tr>
<td class="label">Hippocampus</td>
<td>Medium</td>
</tr>
<tr>
<td class="label">Cortex</td>
<td>Low-Medium</td>
</tr>
<tr>
<td class="label">Cerebellum</td>
<td>Low</td>
</tr>
</table>

Pathway Diagram

Mermaid diagram (expand to render)

Introduction

Gdnf — Glial Cell Line Derived Neurotrophic Factor is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

```{.infobox .infobox-gene} Gene Symbol: GDNF Full Name: Glial Cell Line-Derived Neurotrophic Factor Chromosomal Location: 5p13.2 NCBI Gene ID: 2678 OMIM: 600837 Ensembl ID: ENSG00000144121 UniProt: P39905 (GDNF_HUMAN) Associated Diseases: Parkinson's Disease, Amyotrophic Lateral Sclerosis, Spinal Cord Injury
```

Overview

GDNF (Glial Cell Line-Derived Neurotrophic Factor) is a potent neurotrophic factor critical for dopaminergic neuron survival and peripheral nerve regeneration. [@kordower2000]

Function

Glial Cell Line-Derived Neurotrophic Factor (GDNF) is a potent neurotrophic factor that was originally discovered for its ability to promote the survival of dopaminergic [neurons](/entities/neurons). It belongs to the GDNF family ligands (GFLs), which includes GDNF, neurturin (NRTN), artemin (ARTN), persephin (PSPN), and neublastin (NRTN-like). [@bartus2017]

Normal Function

GDNF signals through a unique receptor complex: [@airaksinen2002]

GFRα1 (GDNF Family Receptor Alpha 1) — primary GDNF-binding receptor
RET (Rearranged during Transfection) — co-receptor with tyrosine kinase activity

This signaling complex activates multiple downstream pathways: [@ibez2007]

PI3K/Akt pathway — promotes neuronal survival
MAPK/ERK pathway — regulates differentiation and plasticity
PLCγ pathway — modulates intracellular calcium

Expression Pattern

GDNF is expressed in:

Striatum
[Hippocampus](/brain-regions/hippocampus)
Cerebral [cortex](/brain-regions/cortex)
Spinal cord
[Astrocytes](/entities/astrocytes) and Schwann cells
Peripheral nervous system

GDNF is particularly important for:

Development and maintenance of dopaminergic neurons
Motor neuron survival
Enteric nervous system development
Kidney development (GDNF is essential for ureteric bud branching)

Disease Associations

Parkinson's Disease

GDNF is the most potent neurotrophic factor for dopaminergic neurons:

Supports survival of substantia nigra pars compacta neurons
Promotes neurite outgrowth and dopamine uptake
Protects against 6-OHDA and MPTP toxicity

Clinical trials: Multiple clinical trials have tested GDNF delivery for PD:

Intracerebral GDNF infusion (failed due to delivery issues)
AAV-GDNF gene therapy (showed safety and promising efficacy)
Continuous delivery methods under development

Challenges:

GDNF does not cross the [blood-brain barrier](/entities/blood-brain-barrier)
Requires direct brain delivery (intraparenchymal or intraventricular)
Retrograde transport from striatum to substantia nigra

Amyotrophic Lateral Sclerosis (ALS)

GDNF supports:

Motor neuron survival
Neuromuscular junction maintenance
Protection against excitotoxicity

Therapeutic potential: AAV-GDNF delivery to motor neurons shows promise in preclinical models.

Spinal Cord Injury

GDNF promotes:

Motor neuron survival after injury
Axonal regeneration
Functional recovery in animal models

Therapeutic Targeting

Key Publications

GDNF: a potent neurotrophic factor for dopaminergic neurons - Nature. 1993. PMID: 7684372(https://pubmed.ncbi.nlm.nih.gov/7684372/)

AAV2-GDNF gene therapy for Parkinson's disease - Mol Ther. 2017. PMID: 28129144(https://pubmed.ncbi.nlm.nih.gov/28129144/)

GDNF and Parkinson's disease - Nat Rev Neurol. 2010. PMID: 20924411(https://pubmed.ncbi.nlm.nih.gov/20924411/)

Neurotrophic factors in ALS - Nat Rev Neurol. 2012. PMID: 22565201(https://pubmed.ncbi.nlm.nih.gov/22565201/)

Cross-Links

[GDNF Protein](/proteins/gdnf)
[Parkinson's Disease](/diseases/parkinsons-disease)
[Amyotrophic Lateral Sclerosis](/diseases/als)
[Dopaminergic Neurons](/entities/dopaminergic-neurons)
[Substantia Nigra](/brain-regions/substantia-nigra)
[Dopaminergic Neurodegeneration](/mechanisms/dopaminergic-neurodegeneration)

External Links

[GDNF Gene - NCBI Gene](https://www.ncbi.nlm.nih.gov/gene/2698)
[GDNF Gene - OMIM](https://www.omim.org/entry/158025)
[GDNF Protein - UniProt](https://www.uniprot.org/uniprot/P39905)
[GDNF Expression - Allen Human Brain Atlas](https://human.brain-map.org/microarray/search/show?search_term=GDNF)

Background

The study of Gdnf — Glial Cell Line Derived Neurotrophic Factor 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.

Brain Atlas Resources

[Allen Human Brain Atlas - gdnf Expression](https://human.brain-map.org/microarray/search/show?search_term=gdnf)
[Allen Cell Type Atlas - gdnf](https://celltypes.brain-map.org/)
[BrainSpan - gdnf Developmental Expression](https://brainspan.org/)
[Allen Mouse Brain Atlas - gdnf](https://mouse.brain-map.org/)

Allen Brain Atlas Data

Gene Expression

GDNF (Glial Cell Line-Derived Neurotrophic Factor) expression patterns:

Substantia nigra - High expression in dopaminergic neurons
Hippocampus - Moderate expression in dentate gyrus
Cerebral cortex - Low-moderate expression
Striatum - Moderate expression

Single-Cell Expression

GDNF is expressed in:

Dopaminergic neurons (TH+, SLC6A3+)
Astrocytes (primary source)
Certain neuronal populations
Schwann cells (peripheral)

Brain Region Expression Levels

References

Lin LF, et al, GDNF: a potent neurotrophic factor for dopaminergic neurons of the substantia nigra (1993)

Kordower JH, et al, Neurodegeneration prevented by lentiviral vector delivery of GDNF in primate models of Parkinson's disease (2000)

Bartus RT, et al, Adeno-associated virus (AAV) gene therapy as a potential treatment for Parkinson's disease: long-term results (2017)

Airaksinen MS, Saarma M, The GDNF family: signalling, biological functions and therapeutic value (2002)

Ibáñez CF, Andressoo JO, Biology of GDNF and its receptors — from neural development to Parkinson's disease (2007)

Pathway Diagram

The following diagram shows the key molecular relationships involving GDNF — Glial Cell Line-Derived Neurotrophic Factor discovered through SciDEX knowledge graph analysis:

Mermaid diagram (expand to render)

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Related Entities

GDNF

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kg_node_id	GDNF
entity_type	gene
origin_type	v1_polymorphic_backfill
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wiki_page_id	wp-06fbb3f65640
__merged_from	{'merged_at': '2026-05-13', 'unprefixed_id': 'genes-gdnf'}
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📊 Evidence Profile Foundational

Evidence Balance

+0%

Certainty

100%

Debates

0

Incoming

79

Outgoing

133

0 supporting 0 contradicting 0 neutral

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📗 Cite This Artifact

GDNF — Glial Cell Line-Derived Neurotrophic Factor

GDNF — Glial Cell Line-Derived Neurotrophic Factor

Pathway Diagram

GDNF — Glial Cell Line-Derived Neurotrophic Factor

Pathway Diagram

Introduction

Overview

Function

Normal Function

Expression Pattern

Disease Associations

Parkinson's Disease

Amyotrophic Lateral Sclerosis (ALS)

Spinal Cord Injury

Therapeutic Targeting

Key Publications

Cross-Links

External Links

Background

Brain Atlas Resources

Allen Brain Atlas Data

Gene Expression

Single-Cell Expression

Brain Region Expression Levels

See Also

References

Pathway Diagram

💬 Discussion