S100A8 - S100 Calcium Binding Protein A8

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S100A8 Gene

Introduction

S100A8 S100 Calcium Binding Protein A8 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"> [@foell2007]
<table> [@kerkhoff2012]
<tr><th colspan="2" style="background:#f0f0f0;">Gene Overview</th></tr> [@lei2020]
<tr><td><strong>Gene Symbol</strong></td><td>S100A8</td></tr> [@horvath2021]
<tr><td><strong>Full Name</strong></td><td>S100 Calcium Binding Protein A8</td></tr> [@vogl2022]
<tr><td><strong>Chromosomal Location</strong></td><td>1q21.3</td></tr> [@chang2021]
<tr><td><strong>Protein Product</strong></td><td>Calgranulin A (Myeloid-related Protein 8, MRP8)</td></tr> [@austermann2022]
<tr><td><strong>Molecular Weight</strong></td><td>~10.8 kDa</td></tr>
<tr><td><strong>Gene Family</strong></td><td>S100 calcium-binding protein family</td></tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/als" style="color:#ef9a9a">ALS</a>, <a href="/wiki/alzheimer" style="color:#ef9a9a">ALZHEIMER</a>, <a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/alzheimer" style="color:#ef9a9a">Alzheimer</a>, <a href="/wiki/atherosclerosis" style="color:#ef9a9a">Atherosclerosis</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">193 edges</a></td>
</tr>
</table>
</div>

Overview

...

S100A8 Gene

Introduction

Overview

The S100A8 gene encodes Calgranulin A, also known as Myeloid-related Protein 8 (MRP8) or S100A8. It is a calcium-binding protein belonging to the S100 family, characterized by two EF-hand calcium-binding motifs. S100A8 forms a heterodimer with S100A9 (MRP14), creating the complex known as calprotectin (S100A8/A9), which serves as a potent antimicrobial agent and damage-associated molecular pattern (DAMP) molecule.

Gene Structure

The S100A8 gene is located in the S100 gene cluster on chromosome 1q21.3, a region prone to genomic rearrangements in various diseases. The gene consists of 3 exons and encodes a 93-amino acid protein. The S100 gene cluster includes at least 13 other S100 genes, many of which are co-expressed in specific cell types and pathological conditions.

Protein Structure

The S100A8 protein contains:

N-terminal hinge region: Low complexity region involved in protein interactions
EF-hand I (pseudo): Non-functional calcium-binding site at N-terminus
EF-hand II (canonical): Functional calcium-binding site at C-terminus
C-terminal tail: Involved in target protein recognition

When complexed with S100A9, S100A8 forms calprotectin, a 24.5 kDa heterodimer with unique biological activities.

Normal Function

S100A8 and the S100A8/A9 complex (calprotectin) have several critical functions:

Antimicrobial activity: Sequesters manganese and zinc, starving pathogens of essential metals

Chemotaxis: Attracts neutrophils to sites of inflammation

Fever induction: Acts as an endogenous pyrogen

[Apoptosis](/entities/apoptosis) regulation: Modulates cell death pathways

Cytoskeletal reorganization: Affects neutrophil motility

Redox balance: Has antioxidant properties

Expression Pattern

S100A8 is primarily expressed in:

Neutrophils: Most abundant S100 protein in neutrophils (40% of cytosolic protein)
Monocytes: Induced during myeloid differentiation
Macrophages: Upregulated in tissue macrophages during inflammation
Epithelial cells: In response to inflammatory cytokines
Certain [neurons](/entities/neurons): Under pathological conditions

Expression is tightly regulated by inflammatory signals, particularly IL-6, TNF-α, and LPS.

Role in Disease

Alzheimer's Disease

S100A8/A9 elevated in AD brain, particularly around amyloid plaques
Expressed by reactive [microglia](/entities/microglia) in AD
Contributes to neuroinflammation through:
[TLR4](/entities/tlr4) receptor activation
[NF-κB](/entities/nf-kb) pathway induction
Pro-inflammatory cytokine production
May promote [Aβ](/proteins/amyloid-beta) aggregation
Potential biomarker: S100A8/A9 in CSF and plasma

Parkinson's Disease

Increased S100A8/A9 in substantia nigra and striatum
Associated with microglial activation
Contributes to dopaminergic neuron death
Found in Lewy bodies
Correlates with disease severity

Amyotrophic Lateral Sclerosis

Upregulated in ALS spinal cord
Produced by activated [microglia](/cell-types/microglia-neuroinflammation) and [astrocytes](/entities/astrocytes)
Contributes to motor neuron injury
Correlates with disease progression
Potential therapeutic target

Multiple Sclerosis

S100A8/A9 a marker of disease activity in MS
Elevated in active lesions
Contributes to demyelination
Predicts relapse risk
Therapeutic targeting in development

Rheumatoid Arthritis

S100A8/A9 established biomarker of disease activity
Produced by inflamed synovium
Drives joint destruction

Therapeutic Implications

| Approach | Status | Notes |
|----------|--------|-------|
| Anti-S100A8/A9 antibodies | Preclinical | Reduces inflammation in models |
| TLR4 inhibitors | Clinical | Downstream of S100A8/A9 |
| Metal chelation | Research | Target metal sequestration |
| Anti-inflammatory drugs | Clinical | Reduce S100A8/A9 induction |

Biomarker Applications

Disease activity marker: S100A8/A9 levels correlate with disease activity in RA, MS, IBD
Treatment response: Changes predict therapeutic response
Prognostic value: Higher levels associated with worse outcomes
CSF biomarker: Potential for neurodegenerative disease diagnosis

Key Research Directions

Receptor identification: Characterizing S100A8/A9 receptors beyond TLR4

Intracellular targets: Understanding nuclear and cytoplasmic functions

Therapeutic modulation: Developing specific inhibitors

Biomarker validation: Large-scale clinical studies

Animal models: Transgenic and knockout studies

Background

The study of S100A8 S100 Calcium Binding Protein A8 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.

External Links

[NCBI Gene - S100A8](https://www.ncbi.nlm.nih.gov/gene)
[UniProt - S100A8](https://www.uniprot.org)
[PubMed](https://pubmed.ncbi.nlm.nih.gov)

References

[Wang S, et al, S100A8/A9 in inflammation and disease (2019)](https://pubmed.ncbi.nlm.nih.gov/31249371/)

[Foell D, et al, S100A8 and S100A9 in inflammatory diseases (2007)](https://pubmed.ncbi.nlm.nih.gov/17721636/)

[Kerkhoff C, et al, S100A8/A9: a key regulator of neutrophil function (2012)](https://pubmed.ncbi.nlm.nih.gov/22959640/)

[Lei L, et al, S100A8/A9 in Alzheimer's disease (2020)](https://pubmed.ncbi.nlm.nih.gov/32988225/)

[Horvath I, et al, S100A8/A9 as biomarker in Parkinson's disease (2021)](https://pubmed.ncbi.nlm.nih.gov/34185892/)

[Vogl T, et al, S100A8/A9: from biochemistry to clinical applications (2022)](https://pubmed.ncbi.nlm.nih.gov/35018867/)

[Chang HJ, et al, Calprotectin in neurological diseases (2021)](https://pubmed.ncbi.nlm.nih.gov/34744956/)

[Austermann J, et al, S100A8/A9: therapeutic target in inflammation (2022)](https://pubmed.ncbi.nlm.nih.gov/35679931/)

Pathway Context

Mermaid diagram (expand to render)

Pathway Diagram

The following diagram shows the key molecular relationships involving S100A8 - S100 Calcium Binding Protein A8 discovered through SciDEX knowledge graph analysis:

Mermaid diagram (expand to render)

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S100A8 - S100 Calcium Binding Protein A8

S100A8 Gene

Introduction

Overview

S100A8 Gene

Introduction

Overview

Gene Structure

Protein Structure

Normal Function

Expression Pattern

Role in Disease

Alzheimer's Disease

Parkinson's Disease

Amyotrophic Lateral Sclerosis

Multiple Sclerosis

Rheumatoid Arthritis

Therapeutic Implications

Biomarker Applications

Key Research Directions

Background

See Also

External Links

References

Pathway Context

Pathway Diagram