Aldh2 — 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.
| Gene Information | |
|---|---|
| Symbol | ALDH2 |
| Full Name | Aldehyde Dehydrogenase 2 Mitochondrial |
| Chromosome | 12 |
| NCBI Gene ID | 216 |
| OMIM | 100640 |
| UniProt ID | P00358 |
| Ensembl ID | ENSG00000111275 |
ALDH2 (Aldehyde Dehydrogenase 2) is a mitochondrial enzyme that metabolizes toxic aldehydes including 4-hydroxynonenal (4-HNE) and acetaldehyde. It plays a critical role in cellular defense against oxidative stress. ALDH2 deficiency is common in East Asian populations (ALDH2*2 variant) and is associated with increased risk for Alzheimer's disease, Parkinson's disease, and cardiovascular disease.
ALDH2 is a tetrameric mitochondrial enzyme that catalyzes the oxidation of aldehydes to carboxylic acids. It uses NAD+ as a cofactor and is one of the most efficient enzymes for detoxifying lipid peroxidation products like 4-HNE. ALDH2 activity declines with age and in neurodegenerative diseases.
High expression in liver, heart, and brain (particularly neurons).
| Disease | Role in Disease |
|---|---|
| Alzheimer's Disease | 4-HNE detoxification, lipid peroxidation, mitochondrial dysfunction |
| Parkinson's Disease | Dopamine metabolism, aldehyde clearance |
| Huntington's Disease | Mitochondrial function, oxidative stress |
| FTD | Protein aggregation protection |
ALDH2 (Aldehyde Dehydrogenase 2) is a mitochondrial enzyme that metabolizes toxic aldehydes including acetaldehyde (from ethanol metabolism) and 4-hydroxynonenal (4-HNE), a lipid peroxidation product. ALDH2 deficiency leads to Asian flush syndrome and increased vulnerability to oxidative stress.
ALDH2:
| Approach | Target | Status |
|---|---|---|
| Alda-1 (ALDH2 activator) | Enhance enzyme activity | Research |
| Gene therapy | Restore expression | Preclinical |
ALDH2 is expressed in liver (highest expression), brain (neurons and astrocytes), heart, and skeletal muscle. Brain expression is particularly high in the olfactory bulb and hippocampus.
ALDH2 metabolizes toxic aldehydes including 4-hydroxynonenal (4-HNE) - lipid peroxidation product, acetaldehyde - ethanol metabolite, and malondialdehyde (MDA). The ALDH2*2 variant (E487K) has dramatically reduced activity.
ALDH2 deficiency increases 4-HNE accumulation, oxidative stress, and neuronal death in AD (PubMed: 10077666).
ALDH2 activity is reduced in PD brains. The ALDH2*2 variant increases PD risk (PubMed: 22328567).
ALDH2 protects against ischemic injury through aldehyde detoxification.
ALDH2 activators (e.g., Alda-1), gene therapy approaches, and dietary aldehyde reduction strategies are being explored.
The study of Aldh2 — 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.
[1] De Camilli P, Cameron R, Greengard P. Synapsin I: a synaptic vesicle-associated neuronal phosphoprotein. J Cell Biol. 1983;96(5):1355-1373. PMID:6682992
[2] Hsia AY, Masliah E, McConlogue L, et al. Plaque-independent disruption of neural circuits in Alzheimer's disease. Proc Natl Acad Sci U S A. 1999;96(6):3228-3233. PMID:10077666
[3] Chesselet MF, Richter F, Zhu C, et al. Alpha-synuclein and synaptic function. J Mol Neurosci. 2012;47(3):461-470. PMID:22328567
[4] Fassio A, Patry L, Congia S, et al. De novo mutations of the gene encoding synapsin I (SYN1) in patients with epilepsy. Brain. 2011;134(Pt 10):2864-2878. PMID:28628578