ALDH1A1 Protein (Aldehyde Dehydrogenase 1A1)

ALDH1A1 Protein (Aldehyde Dehydrogenase 1A1)

<table class="infobox infobox-protein">
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<th class="infobox-header" colspan="2">ALDH1A1 Protein (Aldehyde Dehydrogenase 1A1)</th>
</tr>
<tr>
<td class="label">Symbol</td>
<td><strong>ALDH1A1</strong></td>
</tr>
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<td class="label">Full Name</td>
<td>ALDH1A1 (Aldehyde Dehydrogenase 1A1)</td>
</tr>
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<td class="label">Type</td>
<td>Protein</td>
</tr>
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<td class="label">UniProt</td>
<td><a href="https://www.uniprot.org/uniprot/?query=ALDH1A1" target="_blank">Search UniProt</a></td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/aging" style="color:#ef9a9a">Aging</a>, <a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/cancer" style="color:#ef9a9a">Cancer</a>, <a href="/wiki/carcinoma" style="color:#ef9a9a">Carcinoma</a>, <a href="/wiki/colorectal-cancer" style="color:#ef9a9a">Colorectal Cancer</a></td>
</tr>
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<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">113 edges</a></td>
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</table>

Overview

ALDH1A1 Protein (Aldehyde Dehydrogenase 1A1)

<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">ALDH1A1 Protein (Aldehyde Dehydrogenase 1A1)</th>
</tr>
<tr>
<td class="label">Symbol</td>
<td><strong>ALDH1A1</strong></td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>ALDH1A1 (Aldehyde Dehydrogenase 1A1)</td>
</tr>
<tr>
<td class="label">Type</td>
<td>Protein</td>
</tr>
<tr>
<td class="label">UniProt</td>
<td><a href="https://www.uniprot.org/uniprot/?query=ALDH1A1" target="_blank">Search UniProt</a></td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/aging" style="color:#ef9a9a">Aging</a>, <a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/cancer" style="color:#ef9a9a">Cancer</a>, <a href="/wiki/carcinoma" style="color:#ef9a9a">Carcinoma</a>, <a href="/wiki/colorectal-cancer" style="color:#ef9a9a">Colorectal Cancer</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">113 edges</a></td>
</tr>
</table>

Overview

ALDH1A1 (Aldehyde Dehydrogenase 1 Family, Member A1) is a NAD+-dependent enzyme that catalyzes the oxidation of aldehydes to carboxylic acids [1]. In the brain, ALDH1A1 plays critical roles in detoxifying reactive aldehydes generated during neurotransmitter metabolism, particularly the aldehydes produced from dopamine oxidation [2]. This enzyme is highly expressed in dopaminergic [neurons](/entities/neurons) of the substantia nigra pars compacta and serves as a key protective mechanism against aldehyde-induced neurotoxicity [3]. [@aldha]

bfe67bb53c3c532ef4237fa3323691ae27404769

Structure

ALDH1A1 is a homotetrameric enzyme with each subunit containing: [@hydroxynonenal2017]

• NAD-binding Domain: Binds NAD+ cofactor in a Rossmann fold structure [4]
• Catalytic Domain: Contains the active site with a catalytic cysteine (Cys302) [4]
• Substrate-binding Pocket: Accommodates various aldehyde substrates including retinaldehydes and dopamine-derived aldehydes [5]
• Oligomerization Interface: Mediates tetramer formation essential for enzyme activity [4]

Normal Function

Retinoic Acid Synthesis

ALDH1A1 catalyzes the oxidation of retinaldehyde (vitamin A aldehyde) to retinoic acid, the active form of vitamin A [6]: [@retinoic2019]

• Retinoic acid is a crucial morphogen in embryonic development
• In the adult brain, retinoic acid regulates synaptic plasticity and neurogenesis [7]
• Retinoic acid signaling is implicated in dopaminergic neuron maintenance [8]

Dopamine Metabolism

Following dopamine oxidation, ALDH1A1 detoxifies the resulting aldehydes: [@agerelated2015]

Other Substrates

• 4-Hydroxy-2-nonenal (4-HNE) - lipid peroxidation product
• Acetaldehyde - ethanol metabolite
• Formaldehyde - endogenous aldehyde
• Various aromatic and aliphatic aldehydes [10]

Role in Neurodegenerative Diseases

Parkinson's Disease

ALDH1A1 vulnerability is a hallmark of [Parkinson's disease](/diseases/parkinsons-disease-disease): [@gene2019]

• Selective Loss: ALDH1A1+ dopaminergic neurons in substantia nigra are particularly vulnerable in PD [3]
• Reduced ALDH1A1 Expression: Decreased ALDH1A1 mRNA and protein in PD substantia nigra [11]
• DOPAL Accumulation: Impaired aldehyde detoxification leads to DOPAL accumulation [9]
• Mechanisms: DOPAL promotes [alpha-synuclein](/proteins/alpha-synuclein) aggregation, mitochondrial dysfunction, and neuronal death [12]

Alzheimer's Disease

ALDH1A1 dysregulation is implicated in AD: [@aldhaa]

• Retinoic Acid Signaling Impairment: Reduced ALDH1A1 decreases retinoic acid synthesis [13]
• Oxidative Stress: 4-HNE detoxification is impaired, increasing oxidative damage [14]
• Amyloid Pathology: Retinoic acid deficiency may affect amyloid processing [15]

Aging

• ALDH1A1 activity declines with age in the substantia nigra [16]
• This age-related decline may increase susceptibility to dopaminergic neurodegeneration

Therapeutic Implications

ALDH1A1 as a Therapeutic Target

Biomarker Potential

• ALDH1A1 expression in peripheral blood cells as a PD biomarker [18]
• ALDH1A1 polymorphisms associated with PD risk [19]

Neuroprotective Strategies

• Retinoic acid supplementation to compensate for reduced ALDH1A1
• Antioxidant therapy to reduce aldehyde formation
• MAO-B inhibitors indirectly reduce DOPAL load [20]

See Also

• [ALDH1A1 Gene](/genes/aldh1a1)
• [Parkinson's Disease](/diseases/parkinsons-disease)
• [Alzheimer's Disease](/diseases/alzheimers-disease)
• [Dopamine Metabolism](/mechanisms/dopamine-metabolism)
• [MAO-B Protein](/proteins/maob-protein)

References

External Links

• [UniProt: P00374](https://www.uniprot.org/uniprot/P00374)
• [PDB structures](https://www.rcsb.org/search?q=uniprot:P00374)
• [GeneCards: ALDH1A1](https://www.genecards.org/cgi-bin/carddisp.pl?gene=ALDH1A1)