CCL4 Protein

CCL4 Protein

Introduction

<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">CCL4 Protein</th>
</tr>
<tr>
<td class="label">Protein Name</td>
<td>Chemokine C-C Motif Ligand 4</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>Q14139</td>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>CCL4</td>
</tr>
<tr>
<td class="label">Protein Length</td>
<td>92 amino acids (precursor), 69 aa (mature)</td>
</tr>
<tr>
<td class="label">Molecular Weight</td>
<td>~10 kDa</td>
</tr>
<tr>
<td class="label">Secreted</td>
<td>Yes</td>
</tr>
<tr>
<td class="label">Also Known As</td>
<td>MIP-1β, ACT-2, LAG-1</td>
</tr>
<tr>
<td class="label">Receptor</td>
<td>Affinity</td>
</tr>
<tr>
<td class="label">CCR5</td>
<td>High</td>
</tr>
<tr>
<td class="label">CCR8</td>
<td>Moderate</td>
</tr>
<tr>
<td class="label">Approach</td>
<td>Description</td>
</tr>
<tr>
<td class="label">CCR5 antagonists</td>
<td>Maraviroc (approved for HIV)</td>
</tr>
<tr>
<td class="label">CCL4 neutralizing antibodies</td>
<td>Block CCL4 activity</td>
</tr>
<tr>
<td class="label">Broad-spectrum modulators</td>
<td>Inhibit multiple chemokines</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/autoimmune" style="color:#ef9a9a">Autoimmune</a>, <a href="/wiki/fibrosis" style="color:#ef9a9a">Fibrosis</a>, <a href="/wiki/huntingt

CCL4 Protein

Introduction

<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">CCL4 Protein</th>
</tr>
<tr>
<td class="label">Protein Name</td>
<td>Chemokine C-C Motif Ligand 4</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>Q14139</td>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>CCL4</td>
</tr>
<tr>
<td class="label">Protein Length</td>
<td>92 amino acids (precursor), 69 aa (mature)</td>
</tr>
<tr>
<td class="label">Molecular Weight</td>
<td>~10 kDa</td>
</tr>
<tr>
<td class="label">Secreted</td>
<td>Yes</td>
</tr>
<tr>
<td class="label">Also Known As</td>
<td>MIP-1β, ACT-2, LAG-1</td>
</tr>
<tr>
<td class="label">Receptor</td>
<td>Affinity</td>
</tr>
<tr>
<td class="label">CCR5</td>
<td>High</td>
</tr>
<tr>
<td class="label">CCR8</td>
<td>Moderate</td>
</tr>
<tr>
<td class="label">Approach</td>
<td>Description</td>
</tr>
<tr>
<td class="label">CCR5 antagonists</td>
<td>Maraviroc (approved for HIV)</td>
</tr>
<tr>
<td class="label">CCL4 neutralizing antibodies</td>
<td>Block CCL4 activity</td>
</tr>
<tr>
<td class="label">Broad-spectrum modulators</td>
<td>Inhibit multiple chemokines</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/autoimmune" style="color:#ef9a9a">Autoimmune</a>, <a href="/wiki/fibrosis" style="color:#ef9a9a">Fibrosis</a>, <a href="/wiki/huntington" style="color:#ef9a9a">Huntington</a>, <a href="/wiki/inflammation" style="color:#ef9a9a">Inflammation</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">93 edges</a></td>
</tr>
</table>

Ccl4 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.

Overview

CCL4 (Chemokine C-C Motif Ligand 4), also known as MIP-1β (Macrophage Inflammatory Protein-1 beta), is a CC chemokine that mediates inflammation and immune cell recruitment. It plays important roles in neuroinflammation associated with neurodegenerative diseases. [@reale2019]

Protein Information

Structure

• Signal peptide: 1-23 aa
• Mature protein: 24-92 aa
• Cys-Cys motif: Positions 33-34 (CC chemokine signature)
• Heparin-binding domain: C-terminal region

Molecular Function

Receptor Interactions:

Role in Neurodegeneration

Alzheimer's Disease

• CCL4 protein elevated in AD brain ([hippocampus](/brain-regions/hippocampus), cortex)
• Increased in CSF of AD patients
• Promotes microglial activation and chemotaxis
• Contributes to chronic neuroinflammation
• May have role in amyloid plaque association

Parkinson's Disease

• CCL4 increased in PD substantia nigra
• Attracts [microglia](/cell-types/microglia-neuroinflammation) to dopaminergic [neurons](/entities/neurons)
• Contributes to progressive neuroinflammation
• CSF levels correlate with disease progression

ALS

• CCL4 elevated in ALS spinal cord and CSF
• Promotes inflammatory response in motor neuron environment
• Attracts activated microglia and macrophages
• CCL4 blockade may be therapeutic

HIV-Associated Neurocognitive Disorders

• CCL4 elevated due to HIV infection in brain
• CCR5 is HIV co-receptor - relevance to HAND
• Contributes to chronic neuroinflammation

Therapeutic Targeting

Biomarker Potential

• CCL4 levels in CSF: biomarker for neuroinflammation
• Blood CCL4: potential peripheral marker for disease progression

Interactions

• CCR5: Primary receptor on macrophages, microglia, T cells
• CCR8: Secondary receptor on Th2 and Treg cells
• Proteoglycans: Heparin-binding for gradient formation
• Other chemokines: Can form heterodimers (CCL3-CCL4)

Animal Models

• Ccl4 knockout mice: Reduced inflammation
• Overexpression models: Neuroinflammation phenotype

See Also

• [CCL4 Gene](/proteins/ccl4-protein)
• [Neuroinflammation Pathway](/mechanisms/neuroinflammation-pathway)
• [CCL3 Protein](/proteins/ccl3-protein)
• [CCR5 Protein](/proteins/ccr5-protein)
• [Alzheimer's Disease](/diseases/alzheimers-disease)
• [Parkinson's Disease](/diseases/parkinsons-disease)

Background

The study of Ccl4 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.

External Links

• [PubMed](https://pubmed.ncbi.nlm.nih.gov/) - Biomedical literature
• [Alzheimer's Disease Neuroimaging Initiative](https://adni.loni.usc.edu/) - Research data
• [Allen Brain Atlas](https://brain-map.org/) - Brain gene expression data

References