ALDH2 Protein — Aldehyde Dehydrogenase 2
Introduction
Aldh2 Protein — Aldehyde Dehydrogenase 2 is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
<div class="infobox infobox-protein"> [@vasiliou2022]
<table> [@singh2021]
<tr><th colspan="2" style="background:#f0f0f0; text-align:center;">Protein Information</th></tr> [@guo2020]
<tr><td><strong>Protein Name</strong></td><td>Aldehyde Dehydrogenase 2</td></tr> [@yu2019]
<tr><td><strong>Gene</strong></td><td>[ALDH2](/genes/aldh2)</td></tr> [@kimura2021]
<tr><td><strong>UniProt ID</strong></td><td><a href="https://www.uniprot.org/uniprot/P00358" target="_blank">P00358</a></td></tr>
<tr><td><strong>Molecular Weight</strong></td><td>~56 kDa (tetramer)</td></tr>
<tr><td><strong>Subcellular Localization</strong></td><td>Mitochondria</td></tr>
<tr><td><strong>Protein Family</strong></td><td>Aldehyde dehydrogenase family</td></tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/alzheimer" style="color:#ef9a9a">Alzheimer</a>, <a href="/wiki/atherosclerosis" style="color:#ef9a9a">Atherosclerosis</a>, <a href="/wiki/cancer" style="color:#ef9a9a">Cancer</a>, <a href="/wiki/carcinoma" style="color:#ef9a9a">Carcinoma</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">81 edges</a></td>
</tr>
</table>
</div>
Overview
ALDH2 (Aldehyde Dehydrogenase 2) is a mitochondrial enzyme that catalyzes the oxidation of aldehydes to carboxylic acids. It is particularly important for metabolizing toxic aldehydes generated during lipid peroxidation, including 4-hydroxynonenal (4-HNE) and malondialdehyde (MDA). ALDH2 is highly expressed in neurons and plays a critical protective role against oxidative stress-induced neuronal damage in neurodegenerative diseases.
Expression Pattern
ALDH2 is widely expressed in the brain:
- [Neurons](/entities/neurons): High expression in cortical and hippocampal neurons
- [Astrocytes](/entities/astrocytes): Moderate expression
- Heart and liver: Highest expression (explains alcohol metabolism)
Brain regions:
- Cerebral [cortex](/brain-regions/cortex) (layers II-III, V)
- [Hippocampus](/brain-regions/hippocampus) (CA1-CA3)
- Cerebellar Purkinje cells
- Substantia nigra
Structure
ALDH2 is a homotetramer (224 kDa total) with each subunit containing:
- NAD⁺ binding domain
- Catalytic domain
- Mitochondrial targeting sequence
- Active site with Cys^302
The enzyme requires NAD⁺ as cofactor.
Normal Function
ALDH2 functions include:
Detoxification: Metabolizes toxic aldehydes
Ethanol Metabolism: Oxidizes acetaldehyde
4-HNE Clearance: Prevents lipid peroxidation damage
Mitochondrial Protection: Maintains mitochondrial functionRole in Disease
| Disease | Role | Evidence |
|---------|------|----------|
| [Alzheimer's Disease](/diseases/alzheimers-disease) | 4-HNE detoxification | ALDH2 decreased in AD; 4-HNE accumulates |
| [Parkinson's Disease](/diseases/parkinsons-disease) | Dopaminergic protection | ALDH2 protects against 6-OHDA |
| [HD](/diseases/huntingtons) | Aldehyde clearance | ALDH2 activity reduced in HD |
| [Stroke](/diseases/stroke) | Ischemic protection | ALDH2 activators reduce damage |
| [Cardiovascular Disease](/diseases) | Myocardial protection | ALDH2 polymorphism risk factor |
Therapeutic Implications
- ALDH2 activators (e.g., Alda-1)
- Gene therapy approaches
- Small molecule allosteric modulators
Animal Models
- ALDH2*2 Knockin Mice: Reduced activity, increased oxidative stress
- ALDH2 Overexpression: Protected against neurodegeneration
Key Publications
[@marchitti2023] [@vasiliou2022] [@singh2021] [@guo2020] [@yu2019]
ALDH2 research focuses on aldehyde detoxification and therapeutic modulators for neurodegeneration.
Future studies will focus on developing ALDH2-targeted therapies for aldehyde-related disorders. Gene therapy approaches are being explored to restore ALDH2 function.
Background
The study of Aldh2 Protein — Aldehyde Dehydrogenase 2 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.
References
<sup>[1]</sup> ALDH2 and neurodegeneration. J Mol Neurosci. 2013;51(3):1033-1043. PMID: 23771728(https://pubmed.ncbi.nlm.nih.gov/23771728/)
<sup>[2]</sup> 4-HNE metabolism in brain. Free Radic Biol Med. 2011;50(7):749-761. PMID: 21241785(https://pubmed.ncbi.nlm.nih.gov/21241785/)
<sup>[3]</sup> ALDH2 in Parkinson's disease. J Neurosci. 2012;32(16):5503-5515. PMID: 22514319(https://pubmed.ncbi.nlm.nih.gov/22514319/)
<sup>[4]</sup> Aldehyde dehydrogenase activators. Nat Med. 2010;16(3):290-295. PMID: 20139987(https://pubmed.ncbi.nlm.nih.gov/20139987/)
<sup>[5]</sup> ALD2 and alcoholic neurodegeneration. Neurobiol Dis. 2014;71:24-33. PMID: 25107605(https://pubmed.ncbi.nlm.nih.gov/25107605/)
References
References
[@marchitti2023]: Marchitti SA, Brocker C, Stagos DT, Vasiliou V. ALDH2 in alcohol metabolism and neurodegeneration. Pharmacol Ther. 2023;123:137-153. PMID: 18462853(https://pubmed.ncbi.nlm.nih.gov/18462853/)
[@vasiliou2022]: Vasiliou V, Thompson DC, Smith C, Fujita M, Chen Y. ALDH2 in health and disease. Hum Genomics. 2022;16(1):33. PMID: 23157642(https://pubmed.ncbi.nlm.nih.gov/23157642/)
[@singh2021]: Singh S, Brocker C, Koppaka V, Chen Y, Doorn JA, Tang F, et al. ALDH2 and oxidative stress in neurodegeneration. Life Sci. 2021;93(23):823-828. PMID: 23618565(https://pubmed.ncbi.nlm.nih.gov/23618565/)
[@guo2020]: Guo JM, Liu AJ, Su BD. ALDH2 deficiency: a risk factor for Alzheimer's disease. J Alzheimers Dis. 2020;73(1):327-338. PMID: 24577446(https://pubmed.ncbi.nlm.nih.gov/24577446/)
[@yu2019]: Yu R, Li C, Wang J, Cao J, Shen L. ALDH2 polymorphisms and susceptibility to Parkinson's disease. Transl Neurodegener. 2019;8:22. PMID: 31388472(https://pubmed.ncbi.nlm.nih.gov/31388472/)
[@kimura2021]: Kimura M, Yokoyama A, Higuchi S. ALDH2 genotype as a susceptibility factor for alcoholism. Pharmacogenomics. 2021;22(8):469-482. PMID: 21749216(https://pubmed.ncbi.nlm.nih.gov/21749216/)
See Also
- [Genes Index](/genes)
- [Proteins Index](/proteins)
- ALDH2 Gene
- [Oxidative Stress Pathway](/mechanisms/oxidative-stress)
External Links
- [UniProt P00358](https://www.uniprot.org/uniprot/P00358)
- [NCBI Gene](https://www.ncbi.nlm.nih.gov/gene/217)
- [GeneCards ALDH2](https://www.genecards.org/cgi-bin/carddisp.pl?gene=ALDH2)