S100A8 Protein - Calgranulin A

S100A8 Protein - Calgranulin A

Introduction

<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">S100A8 Protein - Calgranulin A</th>
</tr>
<tr>
<td class="label">Approach</td>
<td>Status</td>
</tr>
<tr>
<td class="label">Anti-S100A8/A9 antibodies</td>
<td>Preclinical</td>
</tr>
<tr>
<td class="label">TLR4 inhibitors</td>
<td>Preclinical</td>
</tr>
<tr>
<td class="label">[RAGE](/entities/rage-receptor) antagonists</td>
<td>Preclinical</td>
</tr>
<tr>
<td class="label">Calcium channel modulators</td>
<td>Research</td>
</tr>
</table>

S100A8 Protein Calgranulin A is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

S100A8 Protein - Calgranulin A

Introduction

<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">S100A8 Protein - Calgranulin A</th>
</tr>
<tr>
<td class="label">Approach</td>
<td>Status</td>
</tr>
<tr>
<td class="label">Anti-S100A8/A9 antibodies</td>
<td>Preclinical</td>
</tr>
<tr>
<td class="label">TLR4 inhibitors</td>
<td>Preclinical</td>
</tr>
<tr>
<td class="label">[RAGE](/entities/rage-receptor) antagonists</td>
<td>Preclinical</td>
</tr>
<tr>
<td class="label">Calcium channel modulators</td>
<td>Research</td>
</tr>
</table>

S100A8 Protein Calgranulin A 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 style="background:#f8f9fa;border:1px solid #ddd;padding:15px;border-radius:5px;margin:10px 0;"> [@alzheimers]
<h3 style="margin-top:0;">S100A8 Protein - Calgranulin A</h3> [@therapeutic]
<table style="width:100%;font-size:14px;"> [@microglial]
<tr><td style="padding:5px;font-weight:bold;">Symbol</td><td style="padding:5px;">S100A8</td></tr> [@biomarker]
<tr><td style="padding:5px;font-weight:bold;">Full Name</td><td style="padding:5px;">S100 Calcium Binding Protein A8</td></tr> [@saa]
<tr><td style="padding:5px;font-weight:bold;">Aliases</td><td style="padding:5px;">Calgranulin A, MRP8, Myeloid-related protein 8</td></tr> [@calprotectin]
<tr><td style="padding:5px;font-weight:bold;">Molecular Weight</td><td style="padding:5px;">10.8 kDa</td></tr> [@tau]
<tr><td style="padding:5px;font-weight:bold;">Protein Family</td><td style="padding:5px;">S100 EF-hand calcium-binding proteins</td></tr>
<tr><td style="padding:5px;font-weight:bold;">Associated Diseases</td><td style="padding:5px;">AD, PD, ALS, MS, Rheumatoid Arthritis, Inflammatory Bowel Disease</td></tr>
</table>
</div>

Overview

S100A8 (S100 Calcium Binding Protein A8), also known as Calgranulin A or Myeloid-Related Protein 8 (MRP8), is a member of the S100 family of EF-hand calcium-binding proteins. It forms a heterodimer with S100A9 (calprotectin) and plays critical roles in inflammation, immune cell recruitment, and neuroinflammation. In the central nervous system, S100A8 is expressed in activated [microglia](/entities/microglia), [astrocytes](/entities/astrocytes), and infiltrating immune cells, where it contributes to the neuroinflammatory cascade observed in neurodegenerative diseases.

Molecular Structure

S100A8 is a small calcium-binding protein (10.8 kDa) containing two EF-hand motifs. The N-terminal EF-hand is a low-affinity calcium-binding site, while the C-terminal EF-hand is a high-affinity binding site. Upon calcium binding, S100A8 undergoes conformational changes that expose hydrophobic regions, enabling protein-protein interactions and dimerization with S100A9.

Molecular Function

Calcium Binding and Dimerization

• Forms S100A8/A9 heterodimer (calprotectin) with S100A9
• Calcium binding induces conformational changes
• Heterodimer formation is required for biological activity

DAMP Function

• Acts as a Damage-Associated Molecular Pattern (DAMP) molecule
• Binds to [TLR4](/entities/tlr4) (Toll-like Receptor 4) on immune cells
• Binds to [RAGE](/genes/rage) (Receptor for Advanced Glycation End-products)
• Activates [NF-κB](/entities/nf-kb) and MAPK signaling pathways
• Promotes pro-inflammatory cytokine production

Immune Cell Functions

• Released from activated neutrophils, monocytes, and [microglia](/cell-types/microglia-neuroinflammation)
• Chemoattractant for immune cell recruitment
• Involved in neutrophil adhesion and migration
• Regulates phagocyte activation and oxidative burst

Expression Pattern

CNS Expression

• Expressed in activated microglia in neurodegenerative conditions
• Astrocytic expression in response to injury
• Perivascular macrophage infiltration
• Low expression in healthy brain, upregulated in disease

Peripheral Expression

• High expression in neutrophils and monocytes
• Released during inflammatory conditions
• Detectable in serum and CSF as biomarker

Role in Disease

Alzheimer's Disease

Parkinson's Disease

Amyotrophic Lateral Sclerosis

Multiple Sclerosis

Therapeutic Targeting

Animal Models

• S100A8 knockout mice show reduced inflammation in autoimmune models
• Transgenic mice overexpressing S100A8 exhibit enhanced neuroinflammation
• Calprotectin administration replicates inflammatory phenotype

Background

The study of S100A8 Protein Calgranulin A 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

• [Neuroinflammation Pathway](/mechanisms/neuroinflammation-pathway)
• [Oxidative Stress Pathway](/mechanisms/oxidative-stress)
• [Alzheimer's Disease](/diseases/alzheimers-disease)
• [Parkinson's Disease](/diseases/parkinsons-disease)
• [Microglia](/cell-types/microglia)
• [TLR4](/entities/tlr4)
• [RAGE](/proteins/rage)

External Links

• [UniProt: S100A8](https://www.uniprot.org/uniprot/P05164)
• [NCBI Protein: S100A8](https://www.ncbi.nlm.nih.gov/protein/NP_001243234)
• [GeneCards: S100A8](https://www.genecards.org/cgi-bin/carddisp.pl?gene=S100A8)
• [OMIM: S100A8](https://www.omim.org/entry/123855)

References