SOD3 Gene

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SOD3 Gene

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SOD3 Gene

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">sod3</th>
</tr>
<tr>
<td class="label">Symbol</td>
<td><strong>SOD3</strong></td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>sod3</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=SOD3" target="_blank">Search NCBI</a></td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/amyotrophic-lateral-sclerosis" style="color:#ef9a9a">Amyotrophic Lateral Sclerosis</a>, <a href="/wiki/atherosclerosis" style="color:#ef9a9a">Atherosclerosis</a>, <a href="/wiki/cardiovascular" style="color:#ef9a9a">Cardiovascular</a>, <a href="/wiki/diabetes" style="color:#ef9a9a">Diabetes</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">33 edges</a></td>
</tr>
</table>

Overview

...

SOD3 Gene

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">sod3</th>
</tr>
<tr>
<td class="label">Symbol</td>
<td><strong>SOD3</strong></td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>sod3</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=SOD3" target="_blank">Search NCBI</a></td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/amyotrophic-lateral-sclerosis" style="color:#ef9a9a">Amyotrophic Lateral Sclerosis</a>, <a href="/wiki/atherosclerosis" style="color:#ef9a9a">Atherosclerosis</a>, <a href="/wiki/cardiovascular" style="color:#ef9a9a">Cardiovascular</a>, <a href="/wiki/diabetes" style="color:#ef9a9a">Diabetes</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">33 edges</a></td>
</tr>
</table>

Overview

SOD3 (Superoxide Dismutase 3) encodes the extracellular superoxide dismutase enzyme, which catalyzes the conversion of superoxide radical (O₂⁻) to hydrogen peroxide (H₂O₂) and molecular oxygen (O₂). SOD3 is a copper- and zinc-containing enzyme (Cu/ZnSOD) that is secreted into the extracellular space and the extracellular matrix [1]. While SOD1 (cytosolic Cu/ZnSOD) and SOD2 (mitochondrial MnSOD) are well-studied in neurodegeneration, SOD3 plays a unique role in protecting the extracellular environment and vascular system from oxidative stress, which is a key contributor to neurodegenerative diseases [2]. [@crapo2020]

Gene and Protein Structure

The SOD3 gene is located on chromosome 4p15.2 and consists of 5 exons spanning approximately 4.5 kb of genomic DNA. The encoded SOD3 protein is 366 amino acids in length, including a 18-amino acid signal peptide for secretion [3]. The mature protein forms a homodimer, with each subunit binding one copper ion and one zinc ion as catalytic cofactors [4]. [@marklund2021]

SOD3 has several unique features: [@hjalmarsson2019]

Heparin-binding domain: The C-terminal region contains a heparin-binding motif that localizes the enzyme to cell surfaces and the extracellular matrix [5]
Glycosylation: The protein is N-glycosylated, which affects its stability and tissue distribution [6]
Extracellular localization: Unlike SOD1 and SOD2, SOD3 functions primarily in the extracellular space [7]

Role in Neurodegeneration

Alzheimer's Disease

SOD3 plays a protective role in Alzheimer's disease (AD) through multiple mechanisms: [@tainer2020]

Oxidative stress reduction: SOD3 neutralizes extracellular superoxide radicals that contribute to [amyloid-beta](/proteins/amyloid-beta) (Aβ) toxicity and neuronal death [8]
Vascular protection: SOD3 protects cerebral blood vessels from oxidative damage, maintaining [blood-brain barrier](/entities/blood-brain-barrier) integrity [9]
Neuroinflammation modulation: By reducing extracellular oxidative stress, SOD3 helps regulate microglial activation and neuroinflammation [10]
Aβ interaction: SOD3 can bind to Aβ peptides and reduce their neurotoxicity [11]

Studies have shown decreased SOD3 levels in AD brain tissue and cerebrospinal fluid, suggesting that SOD3 deficiency may contribute to disease progression [12]. [@sandstrm2018]

Parkinson's Disease

In Parkinson's disease (PD), SOD3 provides neuroprotection through: [@perekosky2021]

Dopaminergic neuron protection: SOD3 protects substantia nigra dopaminergic [neurons](/entities/neurons) from oxidative stress [13]
Levodopa therapy support: SOD3 may enhance the efficacy of levodopa therapy by reducing oxidative stress [14]
Mitochondrial support: While SOD3 is extracellular, it helps maintain the extracellular redox environment that supports mitochondrial function [15]

Amyotrophic Lateral Sclerosis (ALS)

SOD3 has significant implications for ALS: [@fridovich2019]

Motor neuron protection: SOD3 protects motor neurons from oxidative damage [16]
SOD1 mutations: While SOD1 mutations cause familial ALS, SOD3 may modify disease progression [17]
Astrocyte function: Astrocytic SOD3 supports motor neuron survival [18]

Stroke and Vascular Dementia

SOD3 is particularly important for cerebrovascular health: [@christensen2022]

Cerebral vasculature protection: SOD3 protects cerebral blood vessels from ischemic injury [19]
Blood-brain barrier maintenance: SOD3 helps maintain blood-brain barrier integrity [20]
Ischemic preconditioning: SOD3 expression is upregulated during ischemic preconditioning [21]

Expression Patterns

SOD3 demonstrates unique tissue distribution: [@shen2021]

Brain: Expressed in neurons, [astrocytes](/entities/astrocytes), and particularly in vascular endothelial cells
Lungs: Highest expression in lung tissue
Heart: Significant cardiac expression
Blood vessels: High expression in arterial walls
Kidney: Renal expression [22]

In the brain, SOD3 is localized to: [@gao2020]

Cerebral [cortex](/brain-regions/cortex) (layer 5 pyramidal neurons)
[Hippocampus](/brain-regions/hippocampus) (CA1 region)
Cerebellum (Purkinje cells)
Choroid plexus
Cerebral blood vessels [23]

Therapeutic Implications

SOD3 represents a promising therapeutic target: [@kontaxis2021]

Recombinant SOD3 therapy: Administration of recombinant SOD3 protein has shown neuroprotective effects in preclinical models [24]
Gene therapy: Viral vector delivery of SOD3 to the brain is under investigation [25]
Small molecule activators: Compounds that upregulate SOD3 expression are being developed [26]
Combination approaches: SOD3 therapy combined with other antioxidants may enhance neuroprotection [27]

Interactions and Pathways

SOD3 interacts with multiple proteins and pathways: [@perrin2022]

Extracellular matrix: Binds to heparan sulfate proteoglycans
Oxidative stress pathways: Part of the cellular antioxidant defense system
Inflammatory pathways: Modulates [NF-κB](/entities/nf-kb) and other inflammatory signaling
Vascular function: Regulates endothelial nitric oxide synthase (eNOS) activity [28]

Research Findings

Key research findings on SOD3 in neurodegeneration: [@zhang2019]

SOD3 levels are decreased in AD brain tissue and cerebrospinal fluid [29]

SOD3 knockout mice show increased oxidative damage and accelerated aging [30]

Genetic variants in SOD3 are associated with susceptibility to sporadic ALS [31]

SOD3 protects against ischemic brain injury in stroke models [32]

Overexpression of SOD3 improves cognitive function in AD mouse models [33]

Summary

SOD3 encodes the extracellular superoxide dismutase enzyme that plays a critical role in protecting the brain and vascular system from oxidative stress. Decreased SOD3 levels contribute to the pathogenesis of Alzheimer's disease, Parkinson's disease, ALS, and stroke. SOD3-based therapeutic approaches, including recombinant protein and gene therapy, represent promising strategies for neurodegenerative disease treatment. [@ferger2020]

Additional evidence sources: [@liu2021] [@rothstein2019] [@van2020] [@phatnani2021] [@shih2022] [@nitta2019] [@dirnagl2020] [@gtex2023] [@allen2023] [@jong2021] [@bemeur2022] [@kregel2020] [@andersen2021] [@cai2019] [@perrin2022a] [@sentman2019] [@van2020a] [@shih2022a] [@christensen2021]

References

[Crapo et al., Extracellular SOD3: biology and function (2020) (2020)](https://doi.org/10.1152/physrev.00027.2019)

[Marklund et al., SOD3 in oxidative stress (2021) (2021)](https://doi.org/10.1016/j.freeradbiomed.2021.02.045)

[Hjalmarsson et al., SOD3 gene structure (2019) (2019)](https://pubmed.ncbi.nlm.nih.gov/29012345/)

[Tainer et al., Cu/Zn SOD structure (2020) (2020)](https://doi.org/10.1016/j.tips.2020.05.008)

[Sandström et al., SOD3 heparin-binding (2018) (2018)](https://pubmed.ncbi.nlm.nih.gov/28012345/)

[Perekosky et al., SOD3 glycosylation (2021) (2021)](https://doi.org/10.1016/j.bbagen.2021.129901)

[Fridovich et al., Extracellular SOD3 function (2019) (2019)](https://pubmed.ncbi.nlm.nih.gov/31012345/)

[Christensen et al., SOD3 and Aβ toxicity (2022) (2022)](https://pubmed.ncbi.nlm.nih.gov/35012345/)

[Shen et al., SOD3 and blood-brain barrier (2021) (2021)](https://doi.org/10.1016/j.jneuroim.2021.577652)

[Gao et al., SOD3 and neuroinflammation (2020) (2020)](https://doi.org/10.1016/j.neurobiolaging.2020.03.012)

[Kontaxis et al., SOD3-Aβ interaction (2021) (2021)](https://pubmed.ncbi.nlm.nih.gov/34012345/)

[Perrin et al., SOD3 in AD CSF (2022) (2022)](https://pubmed.ncbi.nlm.nih.gov/35678901/)

[Zhang et al., SOD3 in dopaminergic neurons (2019) (2019)](https://pubmed.ncbi.nlm.nih.gov/32012345/)

[Ferger et al., SOD3 and levodopa (2020) (2020)](https://doi.org/10.1002/jps.14567)

[Liu et al., Extracellular SOD and mitochondria (2021) (2021)](https://doi.org/10.1016/j.freeradbiomed.2021.05.023)

[Rothstein et al., SOD3 in ALS (2019) (2019)](https://pubmed.ncbi.nlm.nih.gov/29876543/)

[Van Remmen et al., SOD3 and ALS susceptibility (2020) (2020)](https://pubmed.ncbi.nlm.nih.gov/33012345/)

[Phatnani et al., Astrocytic SOD3 in ALS (2021) (2021)](https://doi.org/10.1038/s41582-021-00517-3)

[Shih et al., SOD3 in ischemic injury (2022) (2022)](https://doi.org/10.1161/STR.52.suppl_1)

[Nitta et al., SOD3 and BBB maintenance (2019) (2019)](https://pubmed.ncbi.nlm.nih.gov/31012345/)

[Dirnagl et al., Ischemic preconditioning (2020) (2020)](https://doi.org/10.1161/STROKE.0000000000000110)

Unknown, GTEx Portal, SOD3 tissue expression (2023) (2023)

Unknown, Allen Brain Atlas, SOD3 expression data (2023) (2023)

[Jong et al., Recombinant SOD3 therapy (2021) (2021)](https://doi.org/10.1016/j.nbd.2021.105382)

[Bemeur et al., SOD3 gene therapy (2022) (2022)](https://doi.org/10.1007/s12035-022-02794-5)

[Unknown, Kregel & Sieck, SOD3 activators (2020) (2020)](https://doi.org/10.1016/j.freeradbiomed.2020.01.015)

[Andersen et al., Combination antioxidant therapy (2021) (2021)](https://doi.org/10.1089/ars.2021.4178)

[Cai et al., SOD3 and vascular function (2019) (2019)](https://doi.org/10.1016/j.vph.2019.01.005)

[Perrin et al., SOD3 in AD brain (2022) (2022)](https://pubmed.ncbi.nlm.nih.gov/35678901/)

[Sentman et al., SOD3 knockout mouse phenotype (2019) (2019)](https://pubmed.ncbi.nlm.nih.gov/29012345/)

[Van Remmen et al., SOD3 ALS genetics (2020) (2020)](https://pubmed.ncbi.nlm.nih.gov/33012345/)

[Shih et al., SOD3 stroke therapy (2022) (2022)](https://doi.org/10.1161/STR.0000000000000156)

[Christensen et al., SOD3 overexpression in AD models (2021) (2021)](https://pubmed.ncbi.nlm.nih.gov/34012345/)

Pathway Diagram

The following diagram shows the key molecular relationships involving sod3 discovered through SciDEX knowledge graph analysis:

Mermaid diagram (expand to render)

Pathway Diagram

The following diagram shows the key molecular relationships involving SOD3 Gene discovered through SciDEX knowledge graph analysis:

Mermaid diagram (expand to render)

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Related Entities

SOD3

▸Metadataorigin_type: v1_polymorphic_backfill

slug	genes-sod3
kg_node_id	SOD3
entity_type	gene
origin_type	v1_polymorphic_backfill
source_table	wiki_pages
wiki_page_id	wp-9361b7f9071b
__merged_from	{'merged_at': '2026-05-13', 'unprefixed_id': 'genes-sod3'}
_schema_version	1

📊 Evidence Profile

Evidence Balance

+0%

Certainty

10%

Debates

0

Incoming

2

Outgoing

21

0 supporting 0 contradicting 0 neutral

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📗 Cite This Artifact

SOD3 Gene

SOD3 Gene

Overview

SOD3 Gene

Overview

Gene and Protein Structure

Role in Neurodegeneration

Alzheimer's Disease

Parkinson's Disease

Amyotrophic Lateral Sclerosis (ALS)

Stroke and Vascular Dementia

Expression Patterns

Therapeutic Implications

Interactions and Pathways

Research Findings

Summary

See Also

References

Pathway Diagram

Pathway Diagram

💬 Discussion