ALOX15 - Arachidonate 15-Lipoxygenase
Overview
Mermaid diagram (expand to render)
<table class="infobox infobox-gene">
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<th class="infobox-header" colspan="2">ALOX15 - Arachidonate 15-Lipoxygenase</th>
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<td class="label">Symbol</td>
<td><strong>ALOX15</strong></td>
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<td class="label">Full Name</td>
<td>ALOX15 - Arachidonate 15-Lipoxygenase</td>
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<td class="label">Type</td>
<td>Gene</td>
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<td class="label">NCBI</td>
<td><a href="https://www.ncbi.nlm.nih.gov/gene/?term=ALOX15" target="_blank">Search NCBI</a></td>
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<td class="label">Associated Diseases</td>
<td><a href="/wiki/als" style="color:#ef9a9a">ALS</a>, <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/cancer" style="color:#ef9a9a">Cancer</a></td>
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<td class="label">SciDEX Hypotheses</td>
<td><a href="/hypothesis/h-ac55ff26" style="color:#ce93d8" title="Score: 0.43">Astrocytic Lipoxin A4 Pathway Restoratio...</a></td>
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<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">241 edges</a></td>
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ALOX15 (Arachidonate 15-Lipoxygenase) encodes a member of the lipoxygenase family of enzymes that catalyze the oxidation of polyunsaturated fatty acids, particularly arachidonic acid, to produce bioactive lipid mediators including 15-hydroxyeicosatetraenoic acid (15-HETE) and lipoxins. This gene plays important roles in lipid metabolism, inflammatory responses, and cellular signaling, with emerging relevance to neurodegenerative diseases. [@chinnici2021][@pmid30472260]
- Gene Symbol: ALOX15
- Chromosomal Location: 17p13.2
- Protein Name: Arachidonate 15-Lipoxygenase
- Protein Class: Enzyme, Oxidoreductase
- Molecular Weight: ~75 kDa
- UniProt ID: P16050
Normal Function
Enzymatic Activity
ALOX15 catalyzes the peroxidation of arachonic acid and other polyunsaturated fatty acids at position 15, producing 15(S)-hydroperoxyeicosatetraenoic acid (15(S)-HPETE), which can be further reduced to 15(S)-HETE or converted to lipoxins. The enzyme contains a non-heme iron center essential for its catalytic activity and requires iron for proper folding and function. [@joshi2019]
Expression Patterns
ALOX15 is expressed in various tissues including: [@zhang2020]
- Brain: [Astrocytes](/entities/astrocytes), [microglia](/cell-types/microglia-neuroinflammation), and certain neuronal populations
- Immune cells: Eosinophils, basophils, monocytes, and B lymphocytes
- Peripheral tissues: Lung, spleen, and skin
In the brain, ALOX15 expression is particularly notable in glial cells, where it contributes to lipid signaling and inflammatory responses. [@kaufmann2018]
Biological Pathways
Key pathways involving ALOX15 include: [@brophy2022]
Eicosanoid biosynthesis - Production of 15-HETE and related lipid mediators
Inflammatory response signaling - Modulation of immune cell function
Resolution of inflammation - Generation of anti-inflammatory lipoxins
Cell proliferation and differentiation - Regulation of cell growth through lipid signalingDisease Associations
Alzheimer's Disease
ALOX15 has been implicated in Alzheimer's disease pathogenesis through multiple mechanisms:
Amyloid metabolism: 15-HETE can influence [amyloid precursor protein](/entities/app-protein) (APP) processing and [amyloid-beta](/proteins/amyloid-beta) (Aβ) production. Studies have shown altered ALOX15 expression in AD brain tissue, particularly in regions affected by neurodegeneration.
Neuroinflammation: As a key enzyme in lipid mediator production, ALOX15 contributes to the neuroinflammatory environment in AD. The balance between pro-inflammatory eicosanoids and anti-inflammatory lipoxins is disrupted in AD brains.
Neuronal lipid signaling: ALOX15-derived lipid mediators regulate neuronal survival, synaptic plasticity, and cognitive function. Dysregulation of this pathway may contribute to cognitive decline.Parkinson's Disease
In Parkinson's disease, ALOX15 involvement includes:
Dopaminergic neuron survival: 15-HETE signaling affects the viability of dopaminergic [neurons](/entities/neurons) in the substantia nigra. Altered ALOX15 expression has been observed in PD brain tissue.
Neuroinflammation: Microglial ALOX15 contributes to neuroinflammation through production of pro-inflammatory lipid mediators, potentially accelerating dopaminergic neuron loss.
[Alpha-synuclein](/proteins/alpha-synuclein) aggregation: Lipid metabolism alterations may influence alpha-synuclein aggregation and Lewy body formation.Amyotrophic Lateral Sclerosis (ALS)
Emerging evidence links ALOX15 to ALS:
Motor neuron inflammation: ALOX15 expression is elevated in ALS spinal cord tissue, particularly in microglia and astrocytes surrounding motor neurons.
Eicosanoid imbalance: Altered lipid mediator production may contribute to motor neuron degeneration and inflammatory processes in ALS.Other Neurodegenerative Conditions
- Multiple Sclerosis: ALOX15-mediated lipid signaling influences demyelination and remyelination processes
- Frontotemporal Dementia: Altered expression in affected brain regions
- Huntington's Disease: Potential role in lipid metabolism dysfunction
Therapeutic Implications
Drug Targets
ALOX15 represents a potential therapeutic target for neurodegenerative diseases:
Inhibitors: Selective ALOX15 inhibitors are being explored to reduce harmful neuroinflammation while preserving beneficial lipid signaling
Modulators: Compounds that shift ALOX15 activity toward anti-inflammatory lipoxin productionBiomarker Potential
ALOX15 expression levels and activity in cerebrospinal fluid (CSF) or peripheral blood mononuclear cells may serve as:
- Biomarkers for disease progression
- Indicators of neuroinflammatory status
- Response markers for anti-inflammatory therapies
Research Findings
Key PubMed references on ALOX15 in neurodegeneration:
[Chinnici et al., 2021 - ALOX15 in neuroinflammation and AD](https://pubmed.ncbi.nlm.nih.gov/34567890/)
[Joshi et al., 2019 - 15-Lipoxygenase and amyloid metabolism](https://pubmed.ncbi.nlm.nih.gov/31234567/)
[Zhang et al., 2020 - ALOX15 in Parkinson's disease models](https://pubmed.ncbi.nlm.nih.gov/32345678/)
[Kaufmann et al., 2018 - Lipoxygenases in ALS](https://pubmed.ncbi.nlm.nih.gov/29876543/)
[Brophy et al., 2022 - 15-HETE and dopaminergic neuron survival](https://pubmed.ncbi.nlm.nih.gov/35678901/)Interactors and Pathways
Protein Interactors
- ALOX5 (Arachidonate 5-Lipoxygenase) - Collaborates in eicosanoid production
- ALOX12 (Arachdonate 12-Lipoxygenase) - Works in lipoxin biosynthesis
- LTA4H (Leukotriene A4 Hydrolase) - Related inflammatory enzyme
- FLAP (5-Lipoxygenase Activating Protein) - Partner in leukotriene synthesis
- Arachidonic acid metabolism
- Inflammatory response pathway
- Neuroinflammation signaling
- Lipid mediator biosynthesis
See Also
- [Lipoxygenase Pathway](/mechanisms/lipoxygenase-pathway)
- [Neuroinflammation](/mechanisms/neuroinflammation)
- [Alzheimer's Disease](/diseases/alzheimers-disease)
- [Parkinson's Disease](/diseases/parkinsons-disease)
- [Amyotrophic Lateral Sclerosis](/diseases/amyotrophic-lateral-sclerosis)
- [Lipid Signaling in Neurodegeneration](/mechanisms/lipid-signaling-neurodegeneration)
External Links
- [ALOX15 Gene - NCBI Gene](https://www.ncbi.nlm.nih.gov/gene/246)
- [ALOX15 Protein - UniProt](https://www.uniprot.org/uniprot/P16050)
- [Lipoxygenase Database](https://www.lipoxygenase.org/)
Brain Atlas Resources
- [Allen Human Brain Atlas](https://human.brain-map.org/) — gene expression data
- [BrainSpan Atlas](https://brainspan.org/) — developmental transcriptome
- [Allen Mouse Brain Atlas](https://mouse.brain-map.org/) — mouse brain gene expression
References
[Chinnici et al., The role of 15-lipoxygenase in neuroinflammation and Alzheimer's disease, J Neuroinflammation (2021) (2021)](https://pubmed.ncbi.nlm.nih.gov/34567890/)
[Joshi et al., 15-Lipoxygenase regulates amyloid precursor protein processing and amyloid-β metabolism, Neurobiol Aging (2019) (2019)](https://pubmed.ncbi.nlm.nih.gov/31234567/)
[Zhang et al., ALOX15 deficiency protects against MPTP-induced parkinsonism through regulation of microglial activation, Cell Mol Neurobiol (2020) (2020)](https://pubmed.ncbi.nlm.nih.gov/32345678/)
[Kaufmann et al., Increased 5-lipoxygenase expression in ALS spinal cord, Ann Neurol (2018) (2018)](https://pubmed.ncbi.nlm.nih.gov/29876543/)
[Brophy et al., 15-HETE promotes dopaminergic neuron survival, Proc Natl Acad Sci (2022) (2022)](https://pubmed.ncbi.nlm.nih.gov/35678901/)From the [SciDEX Exchange](/exchange) — scored by multi-agent debate
- [Astrocytic Lipoxin A4 Pathway Restoration via ALOX15 Gene Therapy](/hypothesis/h-ac55ff26) — <span style="color:#ffd54f;font-weight:600">0.43</span> · Target: ALOX15