Insulin-Like Growth Factor 1 Protein

Insulin-Like Growth Factor 1 Protein

Introduction

Insulin Like Growth Factor 1 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"> [@wrigley2017]
<div class="infobox-header">Insulin-Like Growth Factor 1 (IGF1)</div> [@russo2009]
<div class="infobox-content"> [@carro2002]
<table> [@torresaleman2010]
<tr><th>Protein Name</th><td>Insulin-Like Growth Factor 1</td></tr> [@piriz2011]
<tr><th>Gene</th><td><a href="/genes/igf1">IGF1</a></td></tr> [@flood2022]
<tr><th>UniProt ID</th><td><a href="https://www.uniprot.org/uniprotkb/P05019/entry">P05019</a></td></tr> [@dercole1996]
<tr><th>Molecular Weight</th><td>7.6 kDa (mature peptide)</td></tr>
<tr><th>Subcellular Localization</th><td>Extracellular, Cell Surface</td></tr>
<tr><th>Protein Family</th><td>Insulin-like growth factor family</td></tr>
<tr><th>Associated Diseases</th><td>Alzheimer's Disease, Parkinson's Disease, ALS, Laron Syndrome, Growth Hormone Insensitivity</td></tr>
</table>
</div>
</div>

Overview

Insulin-Like Growth Factor 1 (IGF1) is a 70-amino acid peptide hormone that plays crucial roles in growth, development, and cellular survival. In the brain, IGF1 acts as a potent neurotrophic factor promoting neuronal survival, synaptic plasticity, neurogenesis, and myelination. IGF1 is essential for normal brain development and continues to provide neuroprotective effects throughout life.

Structure

Insulin-Like Growth Factor 1 Protein

Introduction

Insulin Like Growth Factor 1 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"> [@wrigley2017]
<div class="infobox-header">Insulin-Like Growth Factor 1 (IGF1)</div> [@russo2009]
<div class="infobox-content"> [@carro2002]
<table> [@torresaleman2010]
<tr><th>Protein Name</th><td>Insulin-Like Growth Factor 1</td></tr> [@piriz2011]
<tr><th>Gene</th><td><a href="/genes/igf1">IGF1</a></td></tr> [@flood2022]
<tr><th>UniProt ID</th><td><a href="https://www.uniprot.org/uniprotkb/P05019/entry">P05019</a></td></tr> [@dercole1996]
<tr><th>Molecular Weight</th><td>7.6 kDa (mature peptide)</td></tr>
<tr><th>Subcellular Localization</th><td>Extracellular, Cell Surface</td></tr>
<tr><th>Protein Family</th><td>Insulin-like growth factor family</td></tr>
<tr><th>Associated Diseases</th><td>Alzheimer's Disease, Parkinson's Disease, ALS, Laron Syndrome, Growth Hormone Insensitivity</td></tr>
</table>
</div>
</div>

Overview

Insulin-Like Growth Factor 1 (IGF1) is a 70-amino acid peptide hormone that plays crucial roles in growth, development, and cellular survival. In the brain, IGF1 acts as a potent neurotrophic factor promoting neuronal survival, synaptic plasticity, neurogenesis, and myelination. IGF1 is essential for normal brain development and continues to provide neuroprotective effects throughout life.

Structure

IGF1 is a single-chain polypeptide with approximately 50% sequence homology to insulin. The protein contains four domains:

• B Domain (residues 1-25): Core binding region
• C Domain (residues 26-33): Connecting peptide (cleaved in mature form)
• A Domain (residues 42-62): Receptor binding region
• D Domain (residues 63-70): C-terminal extension

Normal Function

Neurotrophic Activities

IGF1 exerts multiple protective and restorative effects on [neurons](/entities/neurons):

Systemic Functions

Beyond the CNS, IGF1 regulates:

• Linear growth (GH-dependent)
• Muscle mass maintenance
• Bone metabolism
• Cardiac function
• Glucose homeostasis

Role in Neurodegeneration

Alzheimer's Disease

IGF1 signaling is significantly altered in AD:

• Reduced CSF IGF1: Levels are decreased in AD patients, correlating with cognitive decline
• Impaired Signaling: Post-receptor signaling defects reduce downstream neuroprotective effects
• Amyloid Interaction: [Aβ](/proteins/amyloid-beta) oligomers interfere with IGF1 receptor function
• [Tau](/proteins/tau) Pathology: Hyperphosphorylated [tau](/proteins/tau) disrupts IGF1 signaling cascades
• Therapeutic Potential: IGF1 administration improves cognitive function in AD mouse models

Parkinson's Disease

IGF1 provides neuroprotection for dopaminergic neurons:

• Dopaminergic Protection: IGF1 protects substantia nigra neurons from 6-OHDA and MPTP toxicity
• [α-Synuclein](/proteins/alpha-synuclein) Modulation: May reduce α-synuclein aggregation
• Mitochondrial Function: Enhances mitochondrial biogenesis and function
• Clinical Trials: Recombinant IGF1 (Ibutamoren) has been tested in PD patients

Amyotrophic Lateral Sclerosis (ALS)

IGF1 has been investigated extensively in ALS:

• Motor Neuron Protection: Promotes survival of upper and lower motor neurons
• Neuroprotective Signaling: Activates Akt pathway critical for neuronal survival
• Clinical Trials: Intrathecal IGF1 showed mixed results in ALS trials
• Gene Therapy: AAV-mediated IGF1 delivery approaches are under development

Other Neurodegenerative Conditions

• Huntington's Disease: IGF1 improves motor function and reduces mutant [huntingtin](/proteins/huntingtin-protein) toxicity
• Multiple Sclerosis: Promotes remyelination and reduces demyelination
• Peripheral Neuropathy: IGF1 gene therapy shows promise for diabetic neuropathy

Signaling Pathways

PI3K/Akt Pathway

IGF1 binding to IGF1R activates:

• Bad phosphorylation (anti-apoptotic)
• mTORC1 activation (protein synthesis)
• [GSK-3β](/entities/gsk3-beta) inhibition (neuroprotection)
• CREB activation (gene transcription)

MAPK/ERK Pathway

Alternative signaling cascade:

Therapeutic Approaches

Recombinant Protein Therapy

• Mecasermin (Increlex): FDA-approved for GH insensitivity
• Ibutamoren (MK-677): Oral GH secretagogue
• Delivery Challenges: [Blood-brain barrier](/entities/blood-brain-barrier) penetration issues

Gene Therapy

• AAV-mediated IGF1 delivery to CNS
• Targeted neuronal expression
• Viral vector approaches in clinical trials

Small Molecule Modulators

• IGF1R agonists under development
• BBB-penetrant compounds
• Combination approaches

Biomarkers

IGF1 levels serve as biomarkers:

• Serum IGF1: Reflects GH-IGF1 axis function
• CSF IGF1: CNS-specific marker (reduced in AD/PD)
• Therapeutic Monitoring: Used to titrate treatment doses

Animal Models

Knockout Studies

• IGF1 null mice: Severe growth deficiency, neurological deficits
• Neuron-specific knockout: Learning and memory impairments

Transgenic Models

• IGF1 overexpression: Enhanced neurogenesis, improved cognition
• AAV-IGF1 delivery: Protects against various neurotoxins

Background

The study of Insulin Like Growth Factor 1 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

• IGF1 Gene
• [IGF1R Protein](/proteins/igf1r-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
• MAPK/ERK Signaling Pathway

External Links

• [UniProt: IGF1](https://www.uniprot.org/uniprotkb/P05019/entry)
• [NCBI Protein: IGF1](https://www.ncbi.nlm.nih.gov/protein)
• [PDB: IGF1 Structure](https://www.rcsb.org/structure/1BQR)
• [Human IGF1 Gene](https://www.genecards.org/cgi-bin/carddisp.pl?gene=IGF1)

References