RELA (NF-κB p65)

RELA (NF-κB p65)

Introduction

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">RELA (NF-κB p65)</th>
</tr>
<tr>
<td class="label">Symbol</td>
<td><strong>RELA</strong></td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>RELA (NF-κB p65)</td>
</tr>
<tr>
<td class="label">Type</td>
<td>Gene</td>
</tr>
<tr>
<td class="label">NCBI</td>
<td><a href="https://www.ncbi.nlm.nih.gov/gene/?term=RELA" target="_blank">Search NCBI</a></td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/aging" style="color:#ef9a9a">Aging</a>, <a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/alzheimer" style="color:#ef9a9a">Alzheimer</a>, <a href="/wiki/atherosclerosis" style="color:#ef9a9a">Atherosclerosis</a>, <a href="/wiki/breast-cancer" style="color:#ef9a9a">Breast Cancer</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">439 edges</a></td>
</tr>
</table>

RELA (p65) is a critical transcription factor subunit of the [NF-κB](/entities/nf-kb) signaling pathway, playing essential roles in inflammation, cell survival, and neuronal function. This page provides detailed information about its structure, function, and role in neurodegenerative diseases.

[@kaltschmidt2022]
[@mattson2021]

Overview

RELA (NF-κB p65)

Introduction

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">RELA (NF-κB p65)</th>
</tr>
<tr>
<td class="label">Symbol</td>
<td><strong>RELA</strong></td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>RELA (NF-κB p65)</td>
</tr>
<tr>
<td class="label">Type</td>
<td>Gene</td>
</tr>
<tr>
<td class="label">NCBI</td>
<td><a href="https://www.ncbi.nlm.nih.gov/gene/?term=RELA" target="_blank">Search NCBI</a></td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/aging" style="color:#ef9a9a">Aging</a>, <a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/alzheimer" style="color:#ef9a9a">Alzheimer</a>, <a href="/wiki/atherosclerosis" style="color:#ef9a9a">Atherosclerosis</a>, <a href="/wiki/breast-cancer" style="color:#ef9a9a">Breast Cancer</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">439 edges</a></td>
</tr>
</table>

RELA (p65) is a critical transcription factor subunit of the [NF-κB](/entities/nf-kb) signaling pathway, playing essential roles in inflammation, cell survival, and neuronal function. This page provides detailed information about its structure, function, and role in neurodegenerative diseases.

[@kaltschmidt2022]
[@mattson2021]

Overview

RELA (also known as p65) encodes the p65 subunit of the NF-κB transcription factor complex. NF-κB is a key regulator of inflammatory responses, cell survival, and immune function. In the brain, RELA-mediated signaling influences neuronal survival, neuroinflammation, and the pathogenesis of Alzheimer's disease, Parkinson's disease, and other neurodegenerative disorders. [@talley2020]

Function

The RELA gene encodes the p65 subunit of NF-κB, also known as RELA. This protein is the key transcriptional activator of the NF-κB signaling pathway. [@huang2021]

NF-κB Complex

The NF-κB family consists of five members: [@srinivasan2022]

• RELA (p65) - Primary transcriptional activator
• REL (c-Rel) - Lymphoid-specific subunit
• RELB - Inducible subunit
• NF-κB1 (p50/p105) - Constitutive subunit
• NF-κB2 (p52/p100) - Inducible subunit

Functions

• Transcription Activation: p65 is the main transcriptional activator, containing the transactivation domain
• Inflammatory Response: Regulates cytokine and chemokine expression
• Cell Survival: Induces anti-apoptotic genes including Bcl-2, Bcl-xL, and IAPs
• Synaptic Plasticity: Involved in activity-dependent gene expression

Signaling Pathways

RELA is activated by: [@baker2023]

• Pro-inflammatory cytokines (TNF-α, IL-1β)
• Amyloid-beta oligomers
• Oxidative stress
• Pathogen-associated molecular patterns (PAMPs)

Disease Associations

Alzheimer's Disease

RELA/p65 activation in Alzheimer's disease [Alzheimer's Disease](/diseases/alzheimers-disease): [@shih2024]

• Drives neuroinflammation through cytokine transcription
• Activated by [amyloid-beta](/proteins/amyloid-beta) oligomers
• Contributes to disease progression through chronic inflammation
• Regulates genes involved in [tau pathology](/mechanisms/tau-pathology)
• Cross-talks with [BACE1](/genes/bace1) and [APP](/genes/app) processing

Parkinson's Disease

In Parkinson's disease [Parkinson's Disease](/diseases/parkinsons-disease), RELA:

• Mediates inflammatory responses in [microglia](/cell-types/microglia-neuroinflammation)
• Activated by [alpha-synuclein](/proteins/alpha-synuclein) aggregates
• Contributes to dopaminergic neuron loss
• Regulates [LRRK2](/genes/lrrk2)-associated pathways

Amyotrophic Lateral Sclerosis

RELA in ALS [Amyotrophic Lateral Sclerosis](/diseases/amyotrophic-lateral-sclerosis):

• Activated in motor [neurons](/entities/neurons) and glia
• Contributes to neuroinflammation
• May regulate [SOD1](/entities/sod1) and [C9orf72](/genes/c9orf72) toxicity

Multiple Sclerosis

• Central role in demyelination
• Regulates immune cell infiltration
• Targets [myelin](/mechanisms/myelin) repair pathways

Therapeutic Implications

Drug Development

• NF-κB Inhibitors: Various compounds targeting RELA activation
• Natural Compounds: Curcumin, resveratrol modulate NF-κB
• Anti-inflammatory Therapies: Aim to reduce RELA-mediated inflammation

Biomarkers

• CSF NF-κB activity levels studied in AD and PD
• Peripheral blood monocyte activation as indicator

Interactions

RELA interacts with numerous proteins and pathways:

• [IκBα](/proteins/ikbalpha) - Inhibitor protein
• [IKK complex](/proteins/ikk-complex) - Activation kinase
• [P300/CBP](/proteins/p300) - Co-activators
• [HDAC1](/genes/hdac1) - Repressor complex
• [Bcl-2](/proteins/bcl-2) family proteins
• Various [TLR](/genes/tlr4) signaling components

See Also

• [NF-κB Signaling Pathway](/mechanisms/nf-kappa-b-signaling)
• [Neuroinflammation](/mechanisms/neuroinflammation)
• [TLR4 Gene](/genes/tlr4) - Toll-like receptor 4
• [TNF Gene](/genes/tnf) - Tumor necrosis factor

Background

The study of Rela (Nf Κb P65) 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

Pathway Diagram

Related Hypotheses

From the [SciDEX Exchange](/exchange) — scored by multi-agent debate

• [SASP-Mediated Complement Cascade Amplification](/hypothesis/h-58e4635a) — <span style="color:#81c784;font-weight:600">0.73</span> · Target: C1Q/C3
• [Senescence-Activated NAD+ Depletion Rescue](/hypothesis/h-cb833ed8) — <span style="color:#81c784;font-weight:600">0.70</span> · Target: CD38/NAMPT
• [SASP-Driven Aquaporin-4 Dysregulation](/hypothesis/h-807d7a82) — <span style="color:#81c784;font-weight:600">0.68</span> · Target: AQP4
• [SASP-Mediated Cholinergic Synapse Disruption](/hypothesis/h-1acdd55e) — <span style="color:#81c784;font-weight:600">0.65</span> · Target: MMP2/MMP9
• [Senescent Cell Mitochondrial DNA Release](/hypothesis/h-1a34778f) — <span style="color:#ffd54f;font-weight:600">0.60</span> · Target: CGAS/STING1/DNASE2
• [Senescence-Induced Lipid Peroxidation Spreading](/hypothesis/h-7957bb2a) — <span style="color:#ffd54f;font-weight:600">0.57</span> · Target: GPX4/SLC7A11
• [Senescence-Associated Myelin Lipid Remodeling](/hypothesis/h-bb518928) — <span style="color:#ffd54f;font-weight:600">0.54</span> · Target: PLA2G6/PLA2G4A

Related Analyses:

• [Is disrupted sleep a cause or consequence of neurodegeneration? Analyze the bidirectional relationsh](/analysis/SDA-2026-04-02-gap-20260402-003058) &#x1f504;
• [Is disrupted sleep a cause or consequence of neurodegeneration? Analyze the bidirectional relationsh](/analysis/SDA-2026-04-02-gap-20260402-003115) &#x1f504;
• [Senolytic therapy for age-related neurodegeneration](/analysis/SDA-2026-04-01-gap-013) &#x1f504;

Pathway Diagram

The following diagram shows the key molecular relationships involving RELA (NF-κB p65) discovered through SciDEX knowledge graph analysis: