AGER Gene

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AGER Gene

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AGER Gene

Introduction

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">AGER Gene</th>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>AGER</td>
</tr>
<tr>
<td class="label">Protein Name</td>
<td>[RAGE](/genes/rage)</td>
</tr>
<tr>
<td class="label">Chromosome</td>
<td>6p21.3</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>Q15120</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>177</td>
</tr>
<tr>
<td class="label">OMIM</td>
<td>600841</td>
</tr>
<tr>
<td class="label">Approach</td>
<td>Status</td>
</tr>
<tr>
<td class="label">Anti-RAGE antibodies</td>
<td>Preclinical</td>
</tr>
<tr>
<td class="label">RAGE inhibitors</td>
<td>Phase 2 trials</td>
</tr>
<tr>
<td class="label">Decoy receptors</td>
<td>Research</td>
</tr>
<tr>
<td class="label">Isoform</td>
<td>Description</td>
</tr>
<tr>
<td class="label">Full-length RAGE</td>
<td>Membrane-bound, signaling competent</td>
</tr>
<tr>
<td class="label">Soluble RAGE (sRAGE)</td>
<td>Decoy receptor, secreted</td>
</tr>
<tr>
<td class="label">N-truncated RAGE</td>
<td>Lacks transmembrane domain</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/ad" style="color:#ef9a9a">AD</a>, <a href="/wiki/ali" style="color:#ef9a9a">ALI</a>, <a href="/wiki/als" style="color:#ef9a9a">ALS</a>, <a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/alzhe

...

AGER Gene

Introduction

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">AGER Gene</th>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>AGER</td>
</tr>
<tr>
<td class="label">Protein Name</td>
<td>[RAGE](/genes/rage)</td>
</tr>
<tr>
<td class="label">Chromosome</td>
<td>6p21.3</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>Q15120</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>177</td>
</tr>
<tr>
<td class="label">OMIM</td>
<td>600841</td>
</tr>
<tr>
<td class="label">Approach</td>
<td>Status</td>
</tr>
<tr>
<td class="label">Anti-RAGE antibodies</td>
<td>Preclinical</td>
</tr>
<tr>
<td class="label">RAGE inhibitors</td>
<td>Phase 2 trials</td>
</tr>
<tr>
<td class="label">Decoy receptors</td>
<td>Research</td>
</tr>
<tr>
<td class="label">Isoform</td>
<td>Description</td>
</tr>
<tr>
<td class="label">Full-length RAGE</td>
<td>Membrane-bound, signaling competent</td>
</tr>
<tr>
<td class="label">Soluble RAGE (sRAGE)</td>
<td>Decoy receptor, secreted</td>
</tr>
<tr>
<td class="label">N-truncated RAGE</td>
<td>Lacks transmembrane domain</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/ad" style="color:#ef9a9a">AD</a>, <a href="/wiki/ali" style="color:#ef9a9a">ALI</a>, <a href="/wiki/als" style="color:#ef9a9a">ALS</a>, <a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/alzheimer's-disease" style="color:#ef9a9a">Alzheimer's Disease</a></td>
</tr>
<tr>
<td class="label">SciDEX Hypotheses</td>
<td><a href="/hypothesis/h-8f285020" style="color:#ce93d8" title="Score: 0.44">Blocking AGE-RAGE Signaling in Enteric G...</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">31 edges</a></td>
</tr>
</table>

Ager Gene is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

AGER encodes [RAGE](/genes/rage) (Receptor for Advanced Glycation End Products), a pattern recognition receptor involved in inflammation and neurodegeneration. [@srikanth2011]

Overview

Mermaid diagram (expand to render)

Function

[RAGE](/entities/rage-receptor) is a multi-ligand receptor that binds:

Advanced glycation end products (AGEs)
HMGB1 (High Mobility Group Box 1)
S100B protein
Amyloid-beta fibrils
DNA release from damaged cells

Signaling Pathways

[NF-κB](/entities/nf-kb) activation → pro-inflammatory cytokine production
MAPK activation → cellular stress response
RAGE-DIAPH1 → cytoskeletal reorganization
Oxidative stress generation via NADPH oxidase

Role in Neurodegeneration

Alzheimer's Disease

RAGE mediates [Aβ](/proteins/amyloid-beta)-induced neuroinflammation
Elevated RAGE expression in AD brain
RAGE-[Aβ](/proteins/amyloid-beta) interaction enhances neuronal toxicity
Therapeutic target: RAGE inhibitors in development

Parkinson's Disease

RAGE involved in dopaminergic neuron death
Links [alpha-synuclein](/proteins/alpha-synuclein) pathology to inflammation
Elevated in substantia nigra of PD patients

ALS

HMGB1-RAGE signaling in motor neuron disease
Contributes to neuroinflammation

Therapeutic Targeting

Key Publications

Stern D, et al. (2002) "RAGE: a novel target for drug intervention in diabetic complications." Current Opinion in Investigational Drugs*. PMID: 12502350(https://pubmed.ncbi.nlm.nih.gov/12502350/)

Srikanth V, et al. (2011) "Role of advanced glycation end products (RAGE) in the brain and its implications for [Alzheimer's disease](/diseases/alzheimers-disease)." Journal of Alzheimer's Disease. PMID: 21593570(https://pubmed.ncbi.nlm.nih.gov/21593570/)

Casserly I, Topol E (2004) "Convergence of atherosclerosis and Alzheimer's disease: inflammation as a common pathway." Lancet. PMID: 15531297(https://pubmed.ncbi.nlm.nih.gov/15531297/)

Liu R, Gao F, et al. (2021) "RAGE mediates Aβ-induced [tau](/proteins/tau) pathology and synaptic dysfunction." Acta Neuropathologica Communications. PMID: 33910657(https://pubmed.ncbi.nlm.nih.gov/33910657/)

Chen X, et al. (2019) "Targeting RAGE as a therapeutic strategy for neurodegenerative diseases." Drug Discovery Today. PMID: 31734362(https://pubmed.ncbi.nlm.nih.gov/31734362/)

RAGE Structure and Isoforms

The RAGE receptor exists in multiple isoforms:

The extracellular domain contains one V-type (variable) domain and two C-type (constant) domains, responsible for ligand binding.

Ligand Binding and Activation Mechanisms

RAGE activates multiple downstream signaling cascades:

NF-κB pathway: Leads to transcription of pro-inflammatory genes

MAPK pathways: ERK, JNK, and p38 MAPKs are activated

PI3K/Akt pathway: Cell survival and proliferation signals

Rho GTPases: Cytoskeletal dynamics via RAGE-DIAPH1 interaction

Genetic Variants and Disease Risk

Several AGER polymorphisms have been associated with disease risk:

-374T/A polymorphism: Associated with reduced AD risk
G82S polymorphism: Affects ligand binding affinity
Promoter variants: Influence expression levels

Biomarkers

RAGE-related biomarkers for neurodegenerative diseases:

sRAGE levels: Lower in AD and PD patients
HMGB1: Elevated in CSF of AD patients
RAGE expression: Upregulated in affected brain regions

Background

The study of Ager Gene 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.

Brain Atlas Resources

[Allen Human Brain Atlas - ager Expression](https://human.brain-map.org/microarray/search/show?search_term=ager)](/datasets/allen-human-brain-atlas)
[Allen Cell Type Atlas - ager](https://celltypes.brain-map.org/)
[BrainSpan - ager Developmental Expression](https://brainspan.org/)
[Allen Mouse Brain Atlas - ager](https://mouse.brain-map.org/)

External Links

[NCBI Gene: AGER](https://www.ncbi.nlm.nih.gov/gene/177)
[UniProt: RAGE](https://www.uniprot.org/uniprotkb/Q15120)
[OMIM: AGER](https://www.omim.org/entry/600841)
[RAGE in Alzheimer's Disease - Nature Reviews](https://www.nature.com/articles/nrn2970)

External Links

[Allen Brain Atlas](https://brain-map.org/) - Brain gene expression data
[Allen Human Brain Atlas search: AGER Gene](https://human.brain-map.org/search?searchText=AGER%20Gene)](/datasets/allen-human-brain-atlas)
[Allen Mouse Brain Atlas search: AGER Gene](https://mouse.brain-map.org/search/index.html?query=AGER%20Gene)](/datasets/mouse-brain-atlas)
[Allen Brain Map portal search: AGER Gene](https://portal.brain-map.org/search?query=AGER%20Gene)

References

[Stern D, et al, (2002) "RAGE: a novel target for drug intervention." Current Opinion in Investigational Drugs (2002)](https://pubmed.ncbi.nlm.nih.gov/12502350/)

[Srikanth V, et al, (2011) "RAGE and Alzheimer's disease." Journal of Alzheimer's Disease (2011)](https://pubmed.ncbi.nlm.nih.gov/21593570/)

[Unknown, Casserly I, Topol E (2004) "Convergence of atherosclerosis and Alzheimer's disease." Lancet (2004)](https://pubmed.ncbi.nlm.nih.gov/15531297/)

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

[Blocking AGE-RAGE Signaling in Enteric Glia to Prevent Neuroinflammatory Cascade](/hypothesis/h-8f285020) — <span style="color:#ffd54f;font-weight:600">0.49</span> · Target: AGER

Pathway Diagram

The following diagram shows the key molecular relationships involving AGER Gene discovered through SciDEX knowledge graph analysis:

Mermaid diagram (expand to render)

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Related Entities

AGER

▸Metadataorigin_type: v1_polymorphic_backfill

slug	genes-ager
kg_node_id	AGER
entity_type	gene
origin_type	v1_polymorphic_backfill
source_table	wiki_pages
wiki_page_id	wp-894ed30c70c3
__merged_from	{'merged_at': '2026-05-13', 'unprefixed_id': 'genes-ager'}
_schema_version	1

📊 Evidence Profile Foundational

Evidence Balance

+0%

Certainty

100%

Debates

0

Incoming

83

Outgoing

42

0 supporting 0 contradicting 0 neutral

View full evidence profile →

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📗 Cite This Artifact

AGER Gene

AGER Gene

Introduction

AGER Gene

Introduction

Overview

Function

Signaling Pathways

Role in Neurodegeneration

Alzheimer's Disease

Parkinson's Disease

ALS

Therapeutic Targeting

Key Publications

RAGE Structure and Isoforms

Ligand Binding and Activation Mechanisms

Genetic Variants and Disease Risk

Biomarkers

Background

Brain Atlas Resources

External Links

External Links

References

Pathway Diagram

💬 Discussion

📗 Cite This Artifact

AGER Gene

AGER Gene

Introduction

AGER Gene

Introduction

Overview

Function

Signaling Pathways

Role in Neurodegeneration

Alzheimer's Disease

Parkinson's Disease

ALS

Therapeutic Targeting

Key Publications

RAGE Structure and Isoforms

Ligand Binding and Activation Mechanisms

Genetic Variants and Disease Risk

Biomarkers

Background

Brain Atlas Resources

External Links

External Links

References

Related Hypotheses

Pathway Diagram

💬 Discussion