IGF1 Gene

IGF1 Gene

Introduction

Igf1 Gene is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

<div class="infobox infobox-gene"> [@schubert1990]
<div class="infobox-header">IGF1</div> [@wrigley2017]
<div class="infobox-content"> [@dercole1996]
<table> [@carro2000]
<tr><th>Full Name</th><td>IGF-1 (Insulin-like Growth Factor 1, Somatomedin C)</td></tr> [@sonntag2005]
<tr><th>Chromosome</th><td>chr12</td></tr> [@torresaleman2010]
<tr><th>Location</th><td>12q23.2</td></tr> [@bath2013]
<tr><th>NCBI Gene ID</th><td>[3479](https://www.ncbi.nlm.nih.gov/gene/3479)</td></tr>
<tr><th>OMIM</th><td>[147440](https://www.omim.org/entry/147440)</td></tr>
<tr><th>Ensembl</th><td>[ENSG00000117471](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000117471)</td></tr>
<tr><th>UniProt</th><td>[P05019](https://www.uniprot.org/uniprotkb/P05019/entry)</td></tr>
<tr><th>Associated Diseases</th><td>Alzheimer's Disease, Parkinson's Disease, ALS, Huntington's Disease, Laron Syndrome</td></tr>
<tr><th>Protein Class</th><td>Growth Factor, Insulin-like Peptide</td></tr>
<tr><th>Expression</th><td>Brain, Liver, Peripheral tissues</td></tr>
</table>
</div>
</div>

Pathway Diagram

IGF1 Gene

Introduction

Igf1 Gene is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

<div class="infobox infobox-gene"> [@schubert1990]
<div class="infobox-header">IGF1</div> [@wrigley2017]
<div class="infobox-content"> [@dercole1996]
<table> [@carro2000]
<tr><th>Full Name</th><td>IGF-1 (Insulin-like Growth Factor 1, Somatomedin C)</td></tr> [@sonntag2005]
<tr><th>Chromosome</th><td>chr12</td></tr> [@torresaleman2010]
<tr><th>Location</th><td>12q23.2</td></tr> [@bath2013]
<tr><th>NCBI Gene ID</th><td>[3479](https://www.ncbi.nlm.nih.gov/gene/3479)</td></tr>
<tr><th>OMIM</th><td>[147440](https://www.omim.org/entry/147440)</td></tr>
<tr><th>Ensembl</th><td>[ENSG00000117471](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000117471)</td></tr>
<tr><th>UniProt</th><td>[P05019](https://www.uniprot.org/uniprotkb/P05019/entry)</td></tr>
<tr><th>Associated Diseases</th><td>Alzheimer's Disease, Parkinson's Disease, ALS, Huntington's Disease, Laron Syndrome</td></tr>
<tr><th>Protein Class</th><td>Growth Factor, Insulin-like Peptide</td></tr>
<tr><th>Expression</th><td>Brain, Liver, Peripheral tissues</td></tr>
</table>
</div>
</div>

Pathway Diagram

Overview

IGF1 (Insulin-like Growth Factor 1) is a 70-amino acid peptide growth factor that plays essential roles in brain development, neuronal survival, synaptic plasticity, and overall nervous system function. Often called "Somatomedin C," IGF1 is produced both centrally in the brain (by neurons and glia) and peripherally in the liver, with the latter able to cross the blood-brain barrier. IGF1 exerts its effects primarily through the IGF1 receptor (IGF1R), activating the PI3K/Akt and MAPK/ERK signaling cascades that promote cell survival, proliferation, and differentiation. This growth factor has garnered significant attention as a therapeutic target for neurodegenerative diseases due to its potent neuroprotective and neurotrophic properties.

Gene Structure

The IGF1 gene is located on chromosome 12q23.2 and spans approximately 80 kb. The gene consists of 6 exons and produces multiple transcript variants through alternative splicing:

• Class 1 transcripts: Include exon 1, encode the classic IGF-1A and IGF-1B isoforms
• Class 2 transcripts: Include exon 2, produce variants with different N-terminal signal peptides
• Ea isoform: The predominant brain isoform
• Eb isoform: Less abundant, alternative splicing

Protein Structure

The mature IGF1 protein is a 70-amino acid peptide (7.6 kDa) with structural homology to insulin:

• B-domain (residues 1-29): Receptor binding
• C-domain (residues 30-35): Connecting peptide
• A-domain (residues 36-70): Receptor binding
• D-domain: Present in some isoforms

• IGF1R: High affinity, primary signaling receptor
• IR (Insulin Receptor): Lower affinity
• IGF2R: IGF1 binding triggers internalization (no signaling)

Normal Function

Neurodevelopment

• Neuronal proliferation and differentiation
• Axonal growth and guidance
• Synapse formation
• Myelination by oligodendrocytes
• Astrocyte function

Neuroprotection

• Anti-apoptotic: Activates PI3K/Akt pathway, inhibiting caspase activation
• Anti-excitotoxic: Modulates glutamate receptor function
• Antioxidant: Upregulates antioxidant enzymes
• Anti-inflammatory: Reduces microglial activation

Synaptic Plasticity

• Enhances [long-term potentiation](/mechanisms/long-term-potentiation) (LTP)
• Regulates AMPA receptor trafficking
• Promotes dendritic spine formation
• Supports learning and memory

Adult Neurogenesis

• Stimulates proliferation in subventricular zone
• Enhances differentiation
• Improves survival of new neurons

Disease Associations

Alzheimer's Disease

• Reduced IGF1 levels in AD brains
• Impaired PI3K/Akt signaling
• Contributes to synaptic loss
• Therapeutic potential of IGF1 delivery

Parkinson's Disease

• Decreased IGF1 in substantia nigra
• Protects dopaminergic neurons
• IGF1 therapy shows promise in models
• Clinical trials ongoing

Amyotrophic Lateral Sclerosis (ALS)

• Dysregulated IGF1 in ALS patients
• IGF1 gene therapy ( AAV) in trials
• Protects motor neurons
• Modulates neuroinflammation

Huntington's Disease

• IGF1 signaling defects
• Mutant [huntingtin](/proteins/huntingtin-protein) disrupts IGF1 signaling
• Therapeutic targeting in development

Laron Syndrome

• IGF1 deficiency due to GH receptor mutations
• Neurodevelopmental consequences
• IGF1 treatment benefits

Expression Pattern

IGF1 exhibits widespread but region-specific expression:

• High Expression: [Hippocampus](/brain-regions/hippocampus) (CA1-CA3, dentate gyrus), [cortex](/brain-regions/cortex) (layers II-VI), cerebellum (Purkinje cells), olfactory bulb
• Moderate Expression: Basal ganglia, thalamus, hypothalamus
• Cell Types: [Neurons](/entities/neurons), [astrocytes](/entities/astrocytes), oligodendrocytes, [microglia](/entities/microglia)

Molecular Mechanisms

Receptor Activation

• Receptor dimerization
• Autophosphorylation
• Recruitment of adapter proteins ([IRS-1](/entities/irs1)/2, Shc)
• Activation of downstream pathways

PI3K/Akt Pathway

• Akt phosphorylation inhibits pro-apoptotic proteins (Bad, FoxO)
• mTORC1 activation promotes protein synthesis
• [GSK-3β](/entities/gsk3-beta) inhibition protects against [tau](/proteins/tau) pathology

MAPK/ERK Pathway

• Ras/Raf/MEK/ERK cascade
• Gene transcription
• Cell growth and differentiation
• Synaptic plasticity

Signaling Cross-talk

• [mTOR](/entities/mtor): Integration with nutrient signaling
• Notch: Neurodevelopmental cross-talk
• Wnt: Developmental interactions

Therapeutic Implications

Recombinant IGF1

• Mecasermin (Increlex): FDA-approved for GH insensitivity
• Intranasal delivery: Bypasses [BBB](/entities/blood-brain-barrier)
• Subcutaneous administration: Systemic delivery
• Clinical trials: AD, PD, ALS

Gene Therapy

• AAV-IGF1 delivery to brain
• Promising in ALS models
• Ongoing clinical trials

Small Molecule Agonists

• IGF1 mimetics
• IGF1R-selective compounds
• Brain-penetrant options

Combination Strategies

• IGF1 + neurotrophic factors
• IGF1 + stem cell therapy
• IGF1 + anti-amyloid approaches

Animal Models

Knockout Mice

• Complete KO: Perinatal lethal, growth deficiency
• Neuron-specific KO: Learning deficits
• Conditional KO: Age-related neurodegeneration

Transgenic Models

• Overexpression: Enhanced neurogenesis
• Disease models: AD, PD, HD
• Reporter lines

Laron Syndrome Models

• GH receptor knockout
• IGF1 deficiency
• Therapeutic testing

Research Directions

• Brain-penetrant IGF1 mimetics
• Intranasal delivery optimization
• Gene therapy clinical translation
• Biomarker development
• Combination therapy approaches

See Also

• [Alzheimer's Disease](/diseases/alzheimers-disease)
• [Parkinson's Disease](/diseases/parkinsons-disease)
• [Neurotrophic Factors](/therapeutics/neurotrophic-factor-therapy-neurodegeneration)
• [IGF1R Gene](/proteins/igf1r-protein)
• [PI3K/Akt Pathway](/mechanisms/pi3k-akt-pathway)

External Links

• [NCBI Gene: IGF1](https://www.ncbi.nlm.nih.gov/gene/3479)
• [UniProt: IGF1](https://www.uniprot.org/uniprotkb/P05019/entry)
• [Ensembl: IGF1](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000117471)
• [OMIM: IGF1](https://www.omim.org/entry/147440)

Background

The study of Igf1 Gene 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.

Allen Brain Atlas Resources

• Allen Human Brain Atlas: [IGF1 gene expression](https://human.brain-map.org/microarray/search/show?search_term=IGF1)
• Allen Mouse Brain Atlas: [IGF1 expression](https://mouse.brain-map.org/search/index.html?query=IGF1)
• Allen Cell Type Atlas: [Transcriptomic cell type reference](https://portal.brain-map.org/atlases-and-data/rnaseq)
• BrainSpan Atlas: [IGF1 developmental expression](https://www.brainspan.org/rnaseq/search/index.html?search_term=IGF1)

References

Pathway Diagram

The following diagram shows the key molecular relationships involving IGF1 Gene discovered through SciDEX knowledge graph analysis: