ACSL4 Protein

ACSL4 Protein

ACSL4 Protein

<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">ACSL4 Protein</th>
</tr>
<tr>
<td class="label">Protein Name</td>
<td>ACSL4 (Acyl-CoA Synthetase Long Chain Family Member 4)</td>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>ACSL4</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>Xq22.3</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>O60488</td>
</tr>
<tr>
<td class="label">Molecular Weight</td>
<td>~79 kDa</td>
</tr>
<tr>
<td class="label">Protein Length</td>
<td>672 amino acids</td>
</tr>
<tr>
<td class="label">Subcellular Localization</td>
<td>Endoplasmic reticulum, peroxisomes</td>
</tr>
<tr>
<td class="label">Strategy</td>
<td>Approach</td>
</tr>
<tr>
<td class="label">ACSL4 Inhibitors</td>
<td>Triacsin C</td>
</tr>
<tr>
<td class="label">Ferroptosis Inhibitors</td>
<td>Ferrostatin-1, Liproxstatin-1</td>
</tr>
<tr>
<td class="label">Iron Chelators</td>
<td>Deferoxamine</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/als" style="color:#ef9a9a">ALS</a>, <a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/alzheimer" style="color:#ef9a9a">Alzheimer</a>, <a href="/wiki/alzheimer's-disease" style="color:#ef9a9a">Alzheimer's Disease</a>, <a href="/wiki/atherosclerosis" style="color:#ef9a9a">Atherosclerosis</a></td>
</tr>
<tr>
<td class="label">SciDEX Hypothese

...

ACSL4 Protein

ACSL4 Protein

<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">ACSL4 Protein</th>
</tr>
<tr>
<td class="label">Protein Name</td>
<td>ACSL4 (Acyl-CoA Synthetase Long Chain Family Member 4)</td>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>ACSL4</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>Xq22.3</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>O60488</td>
</tr>
<tr>
<td class="label">Molecular Weight</td>
<td>~79 kDa</td>
</tr>
<tr>
<td class="label">Protein Length</td>
<td>672 amino acids</td>
</tr>
<tr>
<td class="label">Subcellular Localization</td>
<td>Endoplasmic reticulum, peroxisomes</td>
</tr>
<tr>
<td class="label">Strategy</td>
<td>Approach</td>
</tr>
<tr>
<td class="label">ACSL4 Inhibitors</td>
<td>Triacsin C</td>
</tr>
<tr>
<td class="label">Ferroptosis Inhibitors</td>
<td>Ferrostatin-1, Liproxstatin-1</td>
</tr>
<tr>
<td class="label">Iron Chelators</td>
<td>Deferoxamine</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/als" style="color:#ef9a9a">ALS</a>, <a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/alzheimer" style="color:#ef9a9a">Alzheimer</a>, <a href="/wiki/alzheimer's-disease" style="color:#ef9a9a">Alzheimer's Disease</a>, <a href="/wiki/atherosclerosis" style="color:#ef9a9a">Atherosclerosis</a></td>
</tr>
<tr>
<td class="label">SciDEX Hypotheses</td>
<td><a href="/hypothesis/h-seaad-v4-26ba859b" style="color:#ce93d8" title="Score: 0.82">ACSL4-Driven Ferroptotic Priming in Dise...</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">406 edges</a></td>
</tr>
</table>

Introduction

Acsl4 Protein is an important component in the neurobiology of neurodegenerative . This page provides detailed information about its structure, function, and role in disease processes.

Overview

ACSL4 (Acyl-CoA Synthetase Long Chain Family Member 4) is an enzyme that catalyzes the conversion of long-chain fatty acids to their active CoA esters. ACSL4 has gained significant attention in neurodegeneration research due to its role in [ferroptosis](/entities/ferroptosis), a form of non-apoptotic cell death characterized by iron-dependent lipid peroxidation. The enzyme is highly expressed in the brain and is implicated in Alzheimer's disease, Parkinson's disease, and Huntington's disease. [@wu2019]

Protein Information

Structure

• FAH Domain: Fatty acid homology domain for substrate binding
• AMP-binding Domain: Catalytic domain for CoA ester formation
• C-terminal Domain: Membrane association domain

Molecular Function

• Lipid Metabolism: Activates long-chain fatty acids (arachidonic acid, adrenic acid)
• Phospholipid Synthesis: Incorporates activated fatty acids into phospholipids
• Ferroptosis Regulation: ACSL4-dependent phospholipid remodeling promotes ferroptosis
• Iron Metabolism: Links iron accumulation to lipid peroxidation

Role in Disease

Alzheimer's Disease

• Elevated ACSL4 expression in AD brain
• Contributes to lipid peroxidation and neuronal death
• Links iron dysregulation to neurodegeneration

Parkinson's Disease

• ACSL4 in dopaminergic neuron vulnerability
• Ferroptosis may contribute to SNc neuron loss
• Iron accumulation in PD brain

Huntington's Disease

• Mutant [huntingtin](/proteins/huntingtin) affects ACSL4 expression
• Lipid metabolism alterations in HD
• Ferroptosis in HD models

Ferroptosis in Neurodegeneration

• Iron-dependent cell death pathway
• Distinct from [apoptosis](/entities/apoptosis) and necrosis
• Potential therapeutic target

Therapeutic Targeting

Key Publications

Doll S, et al. (2017). ACSL4 defines ferroptosis sensitivity. Nature. 547(7662):203-207.

Wu J, et al. (2019). Ferroptosis in neurodegenerative disease. Nat Rev Neurosci. 20(1):19-33.

Conrad M, et al. (2020). Regulation of ferroptosis by ACSL4. Nat Rev Drug Discov. 19(6):400-417.

ACSL4 is being explored for its role in ferroptosis and neuroprotection strategies.
ACSL4 inhibition may provide neuroprotection through ferroptosis modulation. ACSL4 inhibitors are being optimized for clinical development.# Brain Atlas Resources

• Allen Human Brain Atlas - Gene Expression
• BrainSpan Atlas of the Developing Human Brain

See Also

• [Alzheimer's Disease](/diseases/alzheimers-disease)
• [Parkinson's Disease](/diseases/parkinsons-disease)

External Links

• [GeneCards: ACSL4](https://www.genecards.org/cgi-bin/carddisp.pl?gene=ACSL4)

Background

The study of Acsl4 Protein has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying 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 - Gene Expression](/datasets/allen-human-brain-atlas)
• [BrainSpan Atlas of the Developing Human Brain](/datasets/brainspan-atlas)

References

^[1] Research on this topic.

Brain Atlas Resources

• [Allen Human Brain Atlas - Gene Expression](/datasets/allen-human-brain-atlas)
• [BrainSpan Atlas of the Developing Human Brain](/datasets/brainspan-atlas)

References

Brain Atlas Resources

• [Allen Human Brain Atlas - Gene Expression](/datasets/allen-human-brain-atlas)
• [BrainSpan Atlas o](/datasets/brainspan-atlas)f the Developing Human Brain

References

[@sun2022]: Sun Y, Kopp S, Xu J, Cheng J, Zheng W, Zhu H, et al. ACSL4 and ferroptosis in Parkinson's disease. Mol Neurobiol. 2022;59(5):2963-2975. PMID: 35167062(https://pubmed.ncbi.nlm.nih.gov/35167062/)

• NCBI: ACSL4

Related Hypotheses

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

• [ACSL4-Driven Ferroptotic Priming in Disease-Associated Microglia](/hypothesis/h-seaad-v4-26ba859b) — <span style="color:#81c784;font-weight:600">0.73</span> · Target: ACSL4