CCR5 Protein

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CCR5 Protein

Overview

<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">CCR5 Protein</th>
</tr>
<tr>
<td class="label">Symbol</td>
<td>CCR5</td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>C-C Chemokine Receptor Type 5</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>3p21.31</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>1234</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>ENSG00000160791</td>
</tr>
<tr>
<td class="label">UniProt</td>
<td>P51681</td>
</tr>
<tr>
<td class="label">Agent</td>
<td>Mechanism</td>
</tr>
<tr>
<td class="label">Maraviroc</td>
<td>CCR5 antagonist</td>
</tr>
<tr>
<td class="label">Vicriviroc</td>
<td>CCR5 antagonist</td>
</tr>
<tr>
<td class="label">Aplaviroc</td>
<td>CCR5 antagonist</td>
</tr>
<tr>
<td class="label">CCR5 antibodies</td>
<td>Neutralizing antibodies</td>
</tr>
<tr>
<td class="label">CCR5-targeting siRNA</td>
<td>Gene silencing</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/cancer" style="color:#ef9a9a">Cancer</a>, <a href="/wiki/cardiovascular" style="color:#ef9a9a">Cardiovascular</a>, <a href="/wiki/dementia" style="color:#ef9a9a">Dementia</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">109 edg

...

CCR5 Protein

Overview

Ccr5 Protein plays an important role in the study of neurodegenerative diseases. This page provides comprehensive information about this topic, including its mechanisms, significance in disease processes, and therapeutic implications.

Introduction

CCR5 (C-C Chemokine Receptor Type 5) is a G protein-coupled receptor that serves as a major co-receptor for HIV-1 entry and plays crucial roles in immune cell trafficking and neuroinflammation. As a chemokine receptor, CCR5 mediates the recruitment of immune cells to sites of inflammation and is expressed on various cell types in the central nervous system, including [microglia](/cell-types/microglia-neuroinflammation) and astrocytes. Dysregulation of CCR5 signaling contributes to chronic neuroinflammation in neurodegenerative diseases, making it both a therapeutic target and a modulator of disease progression. [@zhou2019]

Gene Information

Protein Structure

CCR5 is a 352-amino acid G protein-coupled receptor (GPCR) with characteristic seven-transmembrane domain architecture:

Molecular weight: ~46 kDa
Structure: 7 transmembrane α-helices connected by 3 extracellular and 3 intracellular loops
N-terminus: Extracellular, heavily glycosylated
C-terminus: Intracellular, involved in G protein coupling
Extracellular loops (ECL1-3): Contain ligand binding sites
Intracellular loops (ICL1-3): Couple to G proteins

The crystal structure (PDB: 5UIW) reveals the binding pockets for both endogenous chemokines and small molecule antagonists like maraviroc. The receptor exists as a monomer and can form homodimers or heterodimers with other chemokine receptors.

Molecular Function

CCR5 functions as a chemokine receptor through the following mechanisms:

Ligand Binding: Binds multiple CC chemokines including:

CCL3 (MIP-1α)
CCL4 (MIP-1β)
CCL5 (RANTES)
CCL3L1 (MIP-1β)

Signal Transduction:

Gαi protein-coupled signaling
Inhibition of adenylate cyclase
Activation of MAPK/ERK pathway
PI3K/Akt signaling

Cellular Effects:

Chemotaxis and cell migration
Immune cell activation
Cytokine production
Cell survival and proliferation

Viral Co-receptor Function:

Primary co-receptor for R5-tropic HIV-1
Entry mechanism for viral fusion
Target for HIV prevention strategies

Expression Pattern

CCR5 is expressed on multiple cell types:

Immune Cells:

T lymphocytes (memory CD4+ and CD8+ T cells)
Monocytes/macrophages
Dendritic cells
Natural killer cells

Central Nervous System:

[Microglia](/entities/microglia) (highly expressed)
[Astrocytes](/entities/astrocytes) (reactive astrocytes)
[Neurons](/entities/neurons) (low expression)
Endothelial cells

In the brain, CCR5 expression increases during neuroinflammation, with highest expression on activated microglia surrounding amyloid plaques in Alzheimer's disease and in the substantia nigra in Parkinson's disease.

Role in Neurodegenerative Diseases

Alzheimer's Disease

Elevated CCR5 expression in AD brain tissue, particularly in microglia
Promotes chronic neuroinflammation through continued immune cell recruitment
Contributes to microglial activation and pro-inflammatory cytokine release
Genetic variants (CCR5-Δ32) may modify AD risk and age of onset
CCR5 signaling may interact with [amyloid-beta](/proteins/amyloid-beta) pathology

Parkinson's Disease

Increased CCR5 expression in substantia nigra dopaminergic neurons
Mediates inflammatory responses in the nigrostriatal pathway
May influence dopaminergic neuron degeneration
CCL5/CCR5 axis implicated in PD pathogenesis
Therapeutic targeting potential for neuroprotection

HIV-Associated Neurocognitive Disorders (HAND)

Primary co-receptor for R5-tropic HIV-1 infection of microglia/macrophages
HIV proteins (gp120, Tat) can dysregulate CCR5 signaling
Neuroinflammation driven by viral proteins through CCR5
CCR5 antagonists may reduce HIV-associated neurotoxicity
Chronic inflammation persists despite antiretroviral therapy

Multiple Sclerosis

CCR5+ T cells infiltrate demyelinating lesions
Contributes to autoimmune inflammation in CNS
CCL5 levels elevated in MS lesions and cerebrospinal fluid
CCR5 blockade may reduce demyelination and disease progression
Genetic variants associated with MS susceptibility

Amyotrophic Lateral Sclerosis

CCR5 expression increased in ALS spinal cord
Microglial activation mediated by CCR5 signaling
Contributes to neuroinflammation in motor neuron disease

Therapeutic Targeting

Neurological Applications:

Potential for neuroprotection in AD and PD
May reduce microglial-mediated inflammation
Combination with antiretroviral therapy for HAND

Animal Models

Ccr5 knockout mice: Viable, altered immune cell trafficking
Transgenic mice: CCR5 overexpression in CNS
MPTP model: CCR5 deletion reduces neuroinflammation
[APP](/entities/app-protein)/PS1 model: CCR5 deficiency affects amyloid pathology

Overview

Background

The study of Ccr5 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

[UniProt: P51681](https://www.uniprot.org/uniprot/P51681)
[PDB: 5UIW](https://www.ebi.ac.uk/pdbe/entry/pdb/5uiw)
[IUPHAR: CCR5](https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=68)
[NCBI Gene: CCR5](https://www.ncbi.nlm.nih.gov/gene/1234)
[Human Protein Atlas: CCR5](https://www.proteinatlas.org/ENSG00000160791-CCR5)

References

[Lim JK et al, (2020) (2020)](https://pubmed.ncbi.nlm.nih.gov/33168027/)

[Zhou Y et al, (2019) (2019)](https://pubmed.ncbi.nlm.nih.gov/31759012/)

[Bakhiet M et al, (2017) (2017)](https://pubmed.ncbi.nlm.nih.gov/28757481/)

[Conductier G et al, (2015) (2015)](https://pubmed.ncbi.nlm.nih.gov/26306872/)

[Mallard J et al, (2014) (2014)](https://pubmed.ncbi.nlm.nih.gov/25218854/)

[Szepanski Z et al, (2013) (2013)](https://pubmed.ncbi.nlm.nih.gov/23934690/)

[Galimberti D et al, (2012) (2012)](https://pubmed.ncbi.nlm.nih.gov/22503163/)

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CCR5 Protein

CCR5 Protein

Overview

CCR5 Protein

Overview

Introduction

Gene Information

Protein Structure

Molecular Function

Expression Pattern

Role in Neurodegenerative Diseases

Alzheimer's Disease

Parkinson's Disease

HIV-Associated Neurocognitive Disorders (HAND)

Multiple Sclerosis

Amyotrophic Lateral Sclerosis

Therapeutic Targeting

Animal Models

Overview

Background

See Also

External Links

References