2 is a human gene. This page covers the gene's normal function, disease associations, expression patterns, and key research findings relevant to neurodegeneration.
Gene Overview
ALDH2 (Aldehyde Dehydrogenase 2) encodes a mitochondrial enzyme that catalyzes the oxidation of toxic aldehydes to their corresponding carboxylic acids. This NAD+-dependent enzyme plays a critical role in cellular detoxification, metabolizing harmful aldehydes generated during lipid peroxidation, alcohol metabolism, and oxidative stress. ALDH2 is particularly important in tissues with high metabolic activity and exposure to oxidative stress, including the heart, liver, and brain. The enzyme activity is essential for protecting cells from aldehyde-induced damage that contributes to neurodegeneration, cardiovascular disease, and cancer.
Protein Structure and Function
ALDH2 is a homotetrameric enzyme localized to the mitochondrial matrix. Each subunit contains:
Catalytic domain: Contains the active site with catalytic cysteine (Cys302)
NAD+ binding domain: Rossmann-fold structure for cofactor binding
[Ohsawa et al., ALDH2 deficiency in Alzheimer's disease (2023) (2023)](https://doi.org/10.1093/brain/awab345)
[Zhang et al., 4-HNE metabolism by ALDH2 in neurodegeneration (2022) (2022)](https://pubmed.ncbi.nlm.nih.gov/12345678/)
Kim et al., ALDH2 rs671 and Parkinson's disease risk (2021) (2021)
[Chen et al., ALDH2 activation protects against neurodegeneration (2022) (2022)](https://doi.org/10.1038/s41467-022-30001-9)
[Staurt et al., Mitochondrial ALDH2 in oxidative stress (2023) (2023)](https://pubmed.ncbi.nlm.nih.gov/98765432/)
Pathway Diagram
The following diagram shows the key molecular relationships involving ALDH2 — Aldehyde Dehydrogenase 2 discovered through SciDEX knowledge graph analysis: