Insulin-Like Growth Factor 1 Receptor Protein

Insulin-Like Growth Factor 1 Receptor Protein

Introduction

Insulin Like Growth Factor 1 Receptor Protein 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-protein"> [@girnita2007]
<div class="infobox-header">Insulin-Like Growth Factor 1 Receptor (IGF1R)</div> [@russo2009]
<div class="infobox-content"> [@cheng2013]
<table> [@bassil2014]
<tr><th>Protein Name</th><td>Insulin-Like Growth Factor 1 Receptor</td></tr> [@cohen2009]
<tr><th>Gene</th><td>[IGF1R](/genes/igf1r)</td></tr> [@llorensmartin2013]
<tr><th>UniProt ID</th><td>[P08069](https://www.uniprot.org/uniprotkb/P08069/entry)</td></tr> [@torresaleman2012]
<tr><th>Molecular Weight</th><td>180 kDa (alpha + beta chains)</td></tr>
<tr><th>Subcellular Localization</th><td>Cell Membrane</td></tr>
<tr><th>Protein Family</th><td>Insulin receptor family, Receptor tyrosine kinases</td></tr>
<tr><th>Associated Diseases</th><td>Alzheimer's Disease, Parkinson's Disease, ALS, Cancer, Laron Syndrome</td></tr>
</table>
</div>
</div>

Overview

The Insulin-Like Growth Factor 1 Receptor (IGF1R) is a transmembrane receptor tyrosine kinase that mediates the cellular effects of IGF1. This receptor is widely expressed in the brain and plays essential roles in neuronal development, synaptic plasticity, and neuroprotection. IGF1R is a critical therapeutic target for neurodegenerative diseases due to its potent neurotrophic effects.

Structure

Insulin-Like Growth Factor 1 Receptor Protein

Introduction

Insulin Like Growth Factor 1 Receptor Protein 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-protein"> [@girnita2007]
<div class="infobox-header">Insulin-Like Growth Factor 1 Receptor (IGF1R)</div> [@russo2009]
<div class="infobox-content"> [@cheng2013]
<table> [@bassil2014]
<tr><th>Protein Name</th><td>Insulin-Like Growth Factor 1 Receptor</td></tr> [@cohen2009]
<tr><th>Gene</th><td>[IGF1R](/genes/igf1r)</td></tr> [@llorensmartin2013]
<tr><th>UniProt ID</th><td>[P08069](https://www.uniprot.org/uniprotkb/P08069/entry)</td></tr> [@torresaleman2012]
<tr><th>Molecular Weight</th><td>180 kDa (alpha + beta chains)</td></tr>
<tr><th>Subcellular Localization</th><td>Cell Membrane</td></tr>
<tr><th>Protein Family</th><td>Insulin receptor family, Receptor tyrosine kinases</td></tr>
<tr><th>Associated Diseases</th><td>Alzheimer's Disease, Parkinson's Disease, ALS, Cancer, Laron Syndrome</td></tr>
</table>
</div>
</div>

Overview

The Insulin-Like Growth Factor 1 Receptor (IGF1R) is a transmembrane receptor tyrosine kinase that mediates the cellular effects of IGF1. This receptor is widely expressed in the brain and plays essential roles in neuronal development, synaptic plasticity, and neuroprotection. IGF1R is a critical therapeutic target for neurodegenerative diseases due to its potent neurotrophic effects.

Structure

IGF1R is a heterotetrameric receptor composed of two α-β subunits:

Extracellular α-Chains (706 aa each)

• Ligand-binding domain: Contains multiple repeats of leucine-rich motifs
• Cysteine-rich regions: Provide structural stability
• Fibronectin type III domains: Facilitate receptor dimerization

Transmembrane β-Chains (626 aa each)

• Single transmembrane helix: Anchors receptor in membrane
• Tyrosine kinase domain: Catalytic core (residues 1085-1281)
• C-terminal tail: Contains regulatory tyrosine residues

Key Structural Features

Normal Function

Neurotrophic Signaling

IGF1R mediates essential neuronal functions:

Signaling Pathways

Primary Pathways

PI3K/Akt Cascade:

• IRS-1/2 recruitment to phosphorylated Tyr 950
• PI3K activation → PIP3 generation
• Akt phosphorylation and activation
• Downstream effects on survival, growth, and metabolism

• Shc/Grb2/Sos complex formation
• Ras-Raf-MEK-ERK activation
• Nuclear transcription activation

Secondary Effects

• mTORC1 activation (protein synthesis)
• [GSK-3β](/entities/gsk3-beta) inhibition ([tau](/proteins/tau) phosphorylation regulation)
• CREB activation (gene transcription)
• [NF-κB](/entities/nf-kb) regulation (inflammation)

Role in Neurodegeneration

Alzheimer's Disease

IGF1R involvement in AD is complex:

• Expression Changes: Altered receptor expression in AD brain regions
• [Aβ](/proteins/amyloid-beta) Interaction: Amyloid-β oligomers disrupt IGF1R signaling
• Insulin Resistance: Shared signaling defects with insulin signaling
• Therapeutic Target: Agonists may restore neuroprotective signaling

Parkinson's Disease

IGF1R provides neuroprotection:

• Dopaminergic Neuron Survival: Receptor protects SNpc [neurons](/entities/neurons)
• Mitochondrial Function: Enhances mitochondrial biogenesis
• [α-Synuclein](/proteins/alpha-synuclein) Clearance: May facilitate protein clearance pathways
• Clinical Studies: IGF1R agonists under investigation

ALS

IGF1R signaling is impaired:

• Motor Neuron Vulnerability: Reduced receptor expression in ALS
• Therapeutic Potential: Gene therapy approaches delivering IGF1
• Combination Therapy: With other neurotrophic factors

Cancer

IGF1R is overexpressed in many cancers:

• Proliferation Signal: Drives cancer cell growth
• Therapeutic Target: Antibodies and TKIs in development
• Resistance Mechanisms: Cancer cells develop IGF1R dependency

Therapeutic Targeting

Agonists

• Recombinant IGF1: Ibutamoren (oral GH secretagogue)
• IGF1 Analogs: Modified peptides with enhanced activity
• Monoclonal Antibodies: Agonistic antibodies in development

Antagonists

• Blocking Antibodies: Prevent ligand binding
• Tyrosine Kinase Inhibitors: Small molecule inhibitors
• IGF1R-specific: Selective vs. IR cross-reactivity

Gene Therapy

• AAV-mediated IGF1R activation
• Neuron-specific expression cassettes
• Combination with neurotrophic factors

Biomarkers

IGF1R as a biomarker:

• Receptor Density: Measured via PET ligands
• Phosphorylation Status: p-IGF1R indicates active signaling
• Expression Levels: Altered in disease states
• Therapeutic Response: Biomarker for treatment efficacy

Animal Models

Knockout Studies

• IGF1R null: Embryonic lethal (growth deficiency)
• Neuron-specific knockout: Neuronal loss, behavioral deficits

Transgenic Models

• IGF1R overexpression: Enhanced neuroprotection
• Dominant negative: Accelerated neurodegeneration

Background

The study of Insulin Like Growth Factor 1 Receptor Protein 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.

See Also

• IGF1R Gene
• [IGF1 Protein](/proteins/igf1-protein)
• [Parkinson's Disease](/diseases/parkinsons-disease)
• [Alzheimer's Disease](/diseases/alzheimers-disease)
• [ALS](/diseases/amyotrophic-lateral-sclerosis)
• [Neurotrophic Factor Therapy](/therapeutics/neurotrophic-factor-therapy)
• PI3K/Akt Signaling Pathway
• Receptor Tyrosine Kinase Signaling

External Links

• [UniProt: IGF1R](https://www.uniprot.org/uniprotkb/P08069/entry)
• [NCBI Protein: IGF1R](https://www.ncbi.nlm.nih.gov/protein)
• [PDB: IGF1R Structure](https://www.rcsb.org/structure/1IGR)
• [Human IGF1R Gene](https://www.genecards.org/cgi-bin/carddisp.pl?gene=IGF1R)

References