ddx58

ddx58

Introduction

Ddx58 Gene (Rig I) is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

--- [@matsui2019]
title: DDX58 Gene (RIG-I) [@zhao2020]
description: DDX58 (DEAD-Box Helicase 58), also known as RIG-I, is a cytoplasmic RNA sensor that initiates innate immune responses and has been implicated in neuroinflammation in neurodegenerative diseases. [@thompson2021]
--- [@lee2022]

ddx58

Introduction

Ddx58 Gene (Rig I) is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

--- [@matsui2019]
title: DDX58 Gene (RIG-I) [@zhao2020]
description: DDX58 (DEAD-Box Helicase 58), also known as RIG-I, is a cytoplasmic RNA sensor that initiates innate immune responses and has been implicated in neuroinflammation in neurodegenerative diseases. [@thompson2021]
--- [@lee2022]

<div class="infobox infobox-gene">
<table>
<tr><th colspan="2" class="infobox-header">DDX58 Gene</th></tr>
<tr><th colspan="2" class="infobox-subheader">DEAD-Box Helicase 58 (RIG-I)</th></tr>
<tr><td class="label">Gene Symbol</td><td>DDX58</td></tr>
<tr><td class="label">Full Name</td><td>DEAD-Box Helicase 58</td></tr>
<tr><td class="label">Alternative Names</td><td>RIG-I, RIGI, RLR-1</td></tr>
<tr><td class="label">Chromosomal Location</td><td>9q34.3</td></tr>
<tr><td class="label">NCBI Gene ID</td><td>[23586](https://www.ncbi.nlm.nih.gov/gene/23586)</td></tr>
<tr><td class="label">OMIM</td><td>[609561](https://www.omim.org/entry/609561)</td></tr>
<tr><td class="label">Ensembl ID</td><td>[ENSG00000107201](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000107201)</td></tr>
<tr><td class="label">UniProt ID</td><td>[O95786](https://www.uniprot.org/uniprot/O95786)</td></tr>
<tr><td class="label">Protein Class</td><td>DEAD-box helicase, Pattern Recognition Receptor</td></tr>
<tr><td class="label">Expression</td><td>Ubiquitous, high in immune cells and brain</td></tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/cancer" style="color:#ef9a9a">Cancer</a>, <a href="/wiki/glioblastoma" style="color:#ef9a9a">Glioblastoma</a>, <a href="/wiki/ms" style="color:#ef9a9a">Ms</a>, <a href="/wiki/senescence" style="color:#ef9a9a">Senescence</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">21 edges</a></td>
</tr>
</table>
</div>

Overview

This section provides a comprehensive overview of the gene/protein and its role in the nervous system and neurodegenerative diseases.

Function

DDX58 (DEAD-Box Helicase 58), commonly known as RIG-I (Retinoic Acid-Inducible Gene I), is a cytoplasmic pattern recognition receptor (PRR) that detects viral RNA and initiates antiviral immune responses. RIG-I is a key component of the innate immune system and has been increasingly recognized for its role in [neuroinflammation](/mechanisms/neuroinflammation) in neurodegenerative diseases.

Molecular Functions

RIG-I performs critical innate immune functions:

• RNA sensing: Recognizes 5' triphosphate double-stranded RNA and viral RNA motifs
• Helicase activity: Unwinds RNA substrates using ATP hydrolysis
• Signal transduction: Activates downstream signaling cascades
• Interferon induction: Triggers type I interferon (IFN-α/β) production
• Antiviral response: Initiates cellular antiviral defenses

Domain Structure

RIG-I contains several functional domains:

• N-terminal caspase activation and recruitment domains (CARDs): For downstream signaling
• Helicase domain: RNA binding and ATP hydrolysis
• C-terminal domain (CTD): RNA recognition and binding
• DEAD box motif: ATP-dependent RNA unwinding

Expression Pattern

RIG-I is expressed throughout the body with particularly high levels in:

Brain Regions

• [Cerebral cortex](/brain-regions/cortex)
• [Hippocampus](/brain-regions/hippocampus)
• [Substantia nigra](/brain-regions/substantia-nigra)
• [Basal ganglia](/brain-regions/basal-ganglia)
• [Cerebellum](/brain-regions/cerebellum)

Cell Types

• [Neurons](/cell-types/neurons) — all major subtypes
• [Microglia](/cell-types/microglia) — high expression
• [Astrocytes](/cell-types/astrocytes)
• [Oligodendrocytes](/cell-types/oligodendrocytes) Endothelial cells (blood-brain barrier)

Disease Associations

Alzheimer's Disease

RIG-I has been implicated in [Alzheimer's disease](/diseases/alzheimers-disease):

• Amyloid-β sensing: RIG-I can recognize amyloid-β aggregates as damage-associated molecular patterns (DAMPs)
• Neuroinflammation: Activates [NF-κB](/mechanisms/nf-kb-signaling-neuroinflammation)) and interferon responses in [microglia](/entities/microglia)
• Synaptic dysfunction: Chronic RIG-I activation affects synaptic plasticity
• Microglial priming: RIG-I contributes to microglial activation in AD brain

Parkinson's Disease

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

• Alpha-synuclein sensing: RIG-I may recognize pathological [alpha-synuclein](/proteins/alpha-synuclein) aggregates
• Dopaminergic neuron vulnerability: RIG-I activation contributes to neuronal death
• Neuroinflammation: Sustained interferon responses in the [substantia nigra](/brain-regions/substantia-nigra)

Amyotrophic Lateral Sclerosis

RIG-I in [ALS](/diseases/amyotrophic-lateral-sclerosis):

• Motor neuron inflammation: Elevated RIG-I in motor [neurons](/entities/neurons) and glia
• RNA metabolism: Interactions with ALS-related RNA-binding proteins
• Immune dysregulation: Contributes to chronic neuroinflammation

Viral-Induced Neurodegeneration

RIG-I plays roles in virus-induced brain disorders:

• Herpesviruses: HSV-1 infection triggers RIG-I responses
• Enteroviruses: EV-D68/D71 and neuroinflammation
• Post-viral syndromes: RIG-I-mediated inflammation in long COVID

Autoimmune Disorders

• Singleton's syndrome: Rare DDX58 mutations cause enhanced interferon signaling
• Aicardi-Goutières syndrome: Similar interferonopathies

Mechanism of Action

Canonical Antiviral Pathway

RIG-I activation follows a well-characterized pathway:

Non-Canonical Functions in Neurodegeneration

In neurodegenerative diseases, RIG-I has additional roles:

• DAMP recognition: Recognizes damage-associated molecular patterns
• Protein aggregate sensing: May directly bind to misfolded protein aggregates
• Microglial activation: Primes [microglia](/cell-types/microglia-neuroinflammation) for inflammatory responses
• Synaptic pruning: Affects complement-mediated synapse elimination

Signaling Pathways

RIG-I activates multiple downstream pathways:

• MAVS-dependent signaling: Mitochondrial antiviral signaling protein
• NF-κB pathway: Pro-inflammatory cytokine production
• IRF pathway: Type I interferon induction
• MAPK pathway: Stress-activated protein kinases

Therapeutic Implications

Biomarkers

RIG-I as a biomarker:

• CSF RIG-I: Elevated in neurodegenerative disease cerebrospinal fluid
• Blood biomarkers: Peripheral RIG-I expression correlates with CNS inflammation
• Disease progression: Levels correlate with clinical severity

Therapeutic Targets

Modulating RIG-I signaling:

• RIG-I antagonists: Small molecules to reduce chronic activation
• MAVS inhibitors: Downstream signaling blockers
• Interferon modulators: Reduce type I interferon responses
• Anti-inflammatory therapies: Target downstream effects

Key Publications

Cross-Links

• [DDX58 Protein (RIG-I Protein](/proteins/ddx58-protein)
• [Innate Immune Signaling](/mechanisms/innate-immune-signaling-ad)
• [Neuroinflammation](/mechanisms/neuroinflammation)
• [Alzheimer's Disease](/diseases/alzheimers-disease)
• [Parkinson's Disease](/diseases/parkinsons-disease-disease)
• [Amyotrophic Lateral Sclerosis](/diseases/amyotrophic-lateral-sclerosis)
• [Microglia](/cell-types/microglia)
• [NF-κB Signaling](/mechanisms/nf-kb-signaling-neuroinflammation))
• [Interferon Response](/mechanisms/interferon-response)
• [Alpha-Synuclein](/proteins/alpha-synuclein)
• [TLR Signaling](/mechanisms/tlr-signaling)

External Links

• [NCBI Gene: DDX58](https://www.ncbi.nlm.nih.gov/gene/23586)
• [UniProt: O95786](https://www.uniprot.org/uniprot/O95786)
• [Ensembl: ENSG00000107201](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000107201)
• [Interferome Database](http://interferome.org/)

Background

The study of Ddx58 Gene (Rig I) 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.

See Also

• [Alzheimer's Disease](/diseases/alzheimers-disease)
• [Amyloid Hypothesis](/mechanisms/amyloid-hypothesis)
• [Tau Pathology](/mechanisms/tau-pathology)
• [Parkinson's Disease](/diseases/parkinsons-disease)
• [Alpha-Synuclein](/mechanisms/alpha-synuclein)

References

Pathway Diagram

The following diagram shows the key molecular relationships involving ddx58 discovered through SciDEX knowledge graph analysis:

Pathway Diagram

The following diagram shows the key molecular relationships involving ddx58 discovered through SciDEX knowledge graph analysis: