TLR8 Protein

TLR8 Protein - Toll-Like Receptor 8

Introduction

Tlr8 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"> [@bsibsi2002]
<table>
<tr><th colspan="2" style="background:#f0f0f0;">Protein Information</th></tr>
<tr><td><strong>Protein Name</strong></td><td>Toll-Like Receptor 8 (TLR8)</td></tr>
<tr><td><strong>Gene</strong></td><td>TLR8</td></tr>
<tr><td><strong>UniProt ID</strong></td><td>Q9NYK5</td></tr>
<tr><td><strong>PDB Structure</strong></td><td>3W3G, 3W3J</td></tr>
<tr><td><strong>Molecular Weight</strong></td><td>~110 kDa</td></tr>
<tr><td><strong>Subcellular Localization</strong></td><td>Endoplasmic Reticulum, Endosomes</td></tr>
<tr><td><strong>Protein Family</strong></td><td>Toll-Like Receptor Family</td></tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/inflammation" style="color:#ef9a9a">Inflammation</a>, <a href="/wiki/ms" style="color:#ef9a9a">Ms</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">21 edges</a></td>
</tr>
</table>
</div>

Overview

...

TLR8 Protein - Toll-Like Receptor 8

Introduction

Tlr8 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"> [@bsibsi2002]
<table>
<tr><th colspan="2" style="background:#f0f0f0;">Protein Information</th></tr>
<tr><td><strong>Protein Name</strong></td><td>Toll-Like Receptor 8 (TLR8)</td></tr>
<tr><td><strong>Gene</strong></td><td>TLR8</td></tr>
<tr><td><strong>UniProt ID</strong></td><td>Q9NYK5</td></tr>
<tr><td><strong>PDB Structure</strong></td><td>3W3G, 3W3J</td></tr>
<tr><td><strong>Molecular Weight</strong></td><td>~110 kDa</td></tr>
<tr><td><strong>Subcellular Localization</strong></td><td>Endoplasmic Reticulum, Endosomes</td></tr>
<tr><td><strong>Protein Family</strong></td><td>Toll-Like Receptor Family</td></tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/inflammation" style="color:#ef9a9a">Inflammation</a>, <a href="/wiki/ms" style="color:#ef9a9a">Ms</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">21 edges</a></td>
</tr>
</table>
</div>

Overview

TLR8 (Toll-Like Receptor 8) is an endosomal pattern recognition receptor that recognizes single-stranded RNA (ssRNA) and synthetic compounds like imidazoquinolines. TLR8 is structurally and functionally related to TLR7 and is expressed primarily in monocytes and neutrophils. It plays important roles in antiviral immunity and has been implicated in inflammatory and neurodegenerative conditions.

Structure

TLR8 is a type I transmembrane protein localized in endosomal compartments:

Domain Architecture

• Signal peptide: N-terminal signal peptide
• Leucine-rich repeats (LRRs): 23 LRR motifs for nucleic acid recognition
• Z-loop: Protease-sensitive region
• Transmembrane domain: Single pass transmembrane helix
• TIR domain: Intracellular signaling domain

Structure-Function

• Recognizes ssRNA in endosomal compartments
• Different ligand specificity than TLR7
• Requires acidic endosomes for activation

Normal Function

TLR8 plays important roles in innate immunity:

Immune Recognition

• ssRNA recognition: Detects viral ssRNA
• Synthetic ligands: Recognizes imidazoquinolines
• Small molecule sensing: Chemical compound recognition

Signaling Pathways

MyD88-dependent pathway: Activates [NF-kB](/entities/nf-kb)

Pro-inflammatory cytokines: TNF-alpha, IL-6, IL-12

MAPK activation: ERK, p38 signaling

Cellular Functions

• Monocyte activation: Pro-inflammatory responses
• Neutrophil function: Enhances phagocytosis
• Immune regulation: Modulates adaptive immunity

Role in Disease

Alzheimer Disease

• TLR8 activation in AD neuroinflammation
• May recognize viral or endogenous RNA
• TLR8+ immune cells in AD brain

Parkinson Disease

• TLR8 recognizes extracellular RNA from dying [neurons](/entities/neurons)
• Contributes to microglial activation in substantia nigra

Rheumatoid Arthritis

• TLR8 overexpressed in RA synovium
• Contributes to joint inflammation

Expression

| Cell Type | Expression Level | Notes |
|----------|-----------------|-------|
| Monocytes | High | Primary expression |
| Neutrophils | High | Myeloid lineage |
| Macrophages | Moderate | Tissue macrophages |
| [Microglia](/cell-types/microglia-neuroinflammation) | Low-Moderate | Brain expression |
| Dendritic Cells | Moderate | Some expression |

Therapeutic Targeting

| Approach | Agent | Status | Notes |
|----------|-------|--------|-------|
| TLR8 Antagonists | CU-CPT8m, C909 | Research | Block signaling |
| Anti-inflammatory | Natural compounds | Preclinical | Pathway modulation |
| Small molecule inhibitors | Various | Investigational | Clinical |

Protein Interactions

• MyD88: Primary adaptor protein
• TIRAP: Adaptor protein
• Mal: Signaling adaptor
• NF-kB: Downstream transcription factor

Background

The study of Tlr8 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

• TLR8 Gene
• [TLR7](/genes/tlr7)
• [Toll-Like Receptors](/mechanisms/toll-like-receptor-signaling)
• [Neuroinflammation](/mechanisms/neuroinflammation-pathway)
• [Microglia](/cell-types/microglia)

External Links

• [UniProt: TLR8](https://www.uniprot.org/uniprot/Q9NYK5)
• [PDB: TLR8](https://www.ebi.ac.uk/pdbe/pdbe-search?targetUrl=http://www.ebi.ac.uk/pdbe/entry/pdb/3w3g)
• [NCBI Protein: TLR8](https://www.ncbi.nlm.nih.gov/protein/51311)

References

Jurk M, Heil F, Vollmer J, et al, Human TLR7 or TLR8 independently confer responsiveness to the antiviral compound R-848 (2002)

Bsibsi M, Ravid R, Gveric D, van Noort JM, Broad expression of Toll-like receptors in the human central nervous system (2002)