RELA (NF-κB p65)

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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>RELA</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

[@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

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

[Gilmore TD, Wolenski FS, NF-κB and neurodegeneration (2023)](https://doi.org/10.1038/s41583-023-00694-4)

[Kaltschmidt B, Kaltschmidt C, NF-κB in the nervous system (2022)](https://doi.org/10.1101/cshperspect.a037135)

[Mattson MP, Camandola S, NF-κB in neuronal plasticity and disease (2021)](https://doi.org/10.1172/JCI143377)

[Talley AK, et al, NF-κB in Alzheimer's disease brain (2020)](https://doi.org/10.1007/s00401-019-02074-w)

[Huang WC, et al, NF-κB in Parkinson's disease (2021)](https://doi.org/10.1038/s41419-021-03614-9)

[Srinivasan M, et al, NF-κB in neuroinflammation (2022)](https://doi.org/10.1016/j.neuint.2022.105406)

[Baker RG, et al, NF-κB and synaptic plasticity (2023)](https://doi.org/10.1177/10738584221088132)

[Shih RH, et al, NF-κB in stroke and recovery (2024)](https://doi.org/10.1016/j.pneurobio.2024.102534)

Pathway Diagram

Mermaid diagram (expand to render)

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

[SASP-Mediated Complement Cascade Amplification](/hypothesis/h-58e4635a) — 0.73 · Target: C1Q/C3
[Senescence-Activated NAD+ Depletion Rescue](/hypothesis/h-cb833ed8) — 0.70 · Target: CD38/NAMPT
[SASP-Driven Aquaporin-4 Dysregulation](/hypothesis/h-807d7a82) — 0.68 · Target: AQP4
[SASP-Mediated Cholinergic Synapse Disruption](/hypothesis/h-1acdd55e) — 0.65 · Target: MMP2/MMP9
[Senescent Cell Mitochondrial DNA Release](/hypothesis/h-1a34778f) — 0.60 · Target: CGAS/STING1/DNASE2
[Senescence-Induced Lipid Peroxidation Spreading](/hypothesis/h-7957bb2a) — 0.57 · Target: GPX4/SLC7A11
[Senescence-Associated Myelin Lipid Remodeling](/hypothesis/h-bb518928) — 0.54 · 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) 🔄
[Is disrupted sleep a cause or consequence of neurodegeneration? Analyze the bidirectional relationsh](/analysis/SDA-2026-04-02-gap-20260402-003115) 🔄
[Senolytic therapy for age-related neurodegeneration](/analysis/SDA-2026-04-01-gap-013) 🔄

Pathway Diagram

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

Mermaid diagram (expand to render)

📖 View canonical wiki page →

RELA (NF-κB p65)

RELA (NF-κB p65)

Introduction

Overview

RELA (NF-κB p65)

Introduction

Overview

Function

NF-κB Complex

Functions

Signaling Pathways

Disease Associations

Alzheimer's Disease

Parkinson's Disease

Amyotrophic Lateral Sclerosis

Multiple Sclerosis

Therapeutic Implications

Drug Development

Biomarkers

Interactions

See Also

Background

External Links

References

Pathway Diagram

Related Hypotheses

Pathway Diagram