C6 Protein

C6 Protein

Overview

C6 Protein

Overview

<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">C6 Protein</th>
</tr>
<tr>
<td class="label">Protein Name</td>
<td>Complement Component 6</td>
</tr>
<tr>
<td class="label">Gene</td>
<td>C6</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>P13671</td>
</tr>
<tr>
<td class="label">Molecular Weight</td>
<td>~120 kDa</td>
</tr>
<tr>
<td class="label">Structure</td>
<td>Single-chain glycoprotein with multiple domains</td>
</tr>
<tr>
<td class="label">Subcellular Localization</td>
<td>Plasma, cell membrane</td>
</tr>
<tr>
<td class="label">Protein Family</td>
<td>[Complement system](/entities/complement-system) (terminal pathway)</td>
</tr>
<tr>
<td class="label">Cell Type</td>
<td>C6 Expression</td>
</tr>
<tr>
<td class="label">Neurons</td>
<td>Low (inducible)</td>
</tr>
<tr>
<td class="label">[Astrocytes](/entities/astrocytes)</td>
<td>Moderate</td>
</tr>
<tr>
<td class="label">[Microglia](/cell-types/microglia-neuroinflammation)</td>
<td>High (activated)</td>
</tr>
<tr>
<td class="label">Oligodendrocytes</td>
<td>Low</td>
</tr>
<tr>
<td class="label">Liver (primary)</td>
<td>Very High</td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>

C6 Protein — Complement Component 6 is a protein that c6 functions exclusively in the terminal complement pathway["@structure2015"][@complement2018]:. This page describes its structure, normal nervous system function, role in neurodegenerative disease, and potential as a therapeutic target.

C6 (Complement Component 6) is a terminal complement protein encoded by the C6 gene. C6 is essential for formation of the membrane attack complex (MAC), which creates pores in target cell membranes. In the nervous system, complement activation and MAC deposition play critical roles in neuroinflammation, synaptic pruning, and neuronal loss in Alzheimer's disease, Parkinson's disease, and ALS["@complement2021"][@terminal2020].

Protein Overview

C6 is a critical component of the terminal complement pathway. Without C6, the MAC cannot form, making C6 essential for complement-mediated cytotoxicity.

Normal Function

C6 functions exclusively in the terminal complement pathway[@structure2015][@complement2018]:

Membrane Attack Complex Formation

C6 plays an essential role in MAC assembly:

MAC Function

The MAC creates transmembrane pores that:

• Cause cell lysis via osmotic swelling
• Activate inflammatory responses
• Trigger cell death pathways

Immune Defense

C6 is essential for:

• Bacterial killing
• Viral clearance
• Immune surveillance
• Tumor surveillance

Role in Neurodegenerative Diseases

Alzheimer's Disease

C6 and the MAC play significant roles in AD pathogenesis[@mac2019][@complement2021a]:

Amyloid plaque deposition:

• MAC localizes to amyloid plaques
• Co-localization with [Aβ40](/proteins/amyloid-beta)/42
• Contribution to plaque-associated toxicity

• MAC deposition on [neurons](/entities/neurons)
• Synaptic loss via complement
• Trojan horse mechanism (peripheral MAC)

• Microglial complement production
• Chronic inflammatory state
• C6 as inflammatory mediator

• C6 polymorphisms and AD risk
• Rare protective variants identified

Parkinson's Disease

C6 contributes to PD through complement activation[@complement2020][@synuclein2021]:

Substantia nigra vulnerability:

• Complement activation in SNc
• MAC deposition on dopaminergic neurons
• Enhanced vulnerability to toxins

• C6 recognizes α-synuclein aggregates
• Complement-dependent opsonization
• Glial phagocytosis enhancement

• Microglial complement activation
• Chronic neuroinflammation
• Progression of pathology

Amyotrophic Lateral Sclerosis

In ALS, C6 and terminal complement are strongly activated[@complement2019][@als2021]:

Motor neuron loss:

• MAC deposition on motor neurons
• Complement-mediated cytotoxicity
• Excitotoxicity amplification

• Astrocytic complement production
• Microglial activation
• Non-cell autonomous toxicity

• Elevated C6 in CSF
• Disease progression marker
• Therapeutic target

Other Neurodegenerative Conditions

• Multiple Sclerosis: Demyelination complement involvement
• Huntington's Disease: Complement in striatal degeneration
• Frontotemporal Dementia: [Tau](/proteins/tau)-complement interactions
• Prion Disease: Prion-complement synergy

Expression and Regulation

C6 expression in the nervous system:

C6 is upregulated by:

• Pro-inflammatory cytokines (IL-1β, TNF-α)
• [Aging](/diseases/aging)
• [Neurodegeneration](/diseases/neurodegeneration)
• Infection

Therapeutic Implications

C6 is a promising therapeutic target[@complement2022][@targeting2021]:

Complement Inhibitors

Clinical development:

• C6-specific antibodies
• Small molecule inhibitors
• Recombinant C6 inhibitors

• Blocking MAC formation
• Reducing neuroinflammation
• Preventing synaptic loss

Drug Candidates

• Eculizumab (C5 inhibitor, approved)
• Ravulizumab (C5 inhibitor)
• C6-specific candidates in development

Research Directions

• [Blood-brain barrier](/entities/blood-brain-barrier) penetration
• Timing of intervention
• Biomarker development
• Combination therapies

Cross-Links

• [C6 Gene](/genes/c6)
• [Complement System](/mechanisms/complement-system-neurodegeneration)
• [Membrane Attack Complex](/mechanisms/membrane-attack-complex)
• [Alzheimer's Disease](/diseases/alzheimers-disease)
• [Parkinson's Disease](/diseases/parkinsons-disease)
• [ALS](/diseases/amyotrophic-lateral-sclerosis)
• [C5 Protein](/proteins/c5)
• [Neuroinflammation](/mechanisms/neuroinflammation)
• [Synaptic Pruning](/mechanisms/synaptic-pruning)

See Also

• [Complement System](/mechanisms/complement-system-neurodegeneration)
• [Membrane Attack Complex](/mechanisms/membrane-attack-complex)
• [Alzheimer's Disease](/diseases/alzheimers-disease)
• [Parkinson's Disease](/diseases/parkinsons-disease)
• [ALS](/diseases/amyotrophic-lateral-sclerosis)
• [Neuroinflammation](/mechanisms/neuroinflammation)
• [Synaptic Pruning](/mechanisms/synaptic-pruning)

External Links

• [PubMed](https://pubmed.ncbi.nlm.nih.gov/)
• [KEGG Pathways](https://www.genome.jp/kegg/pathway.html)

References