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Background: Aldehyde Dehydrogenase 2 (ALDH2) is a mitochondrial dehydrogenase enzyme primarily tasked with the detoxification of acetaldehyde produced from alcohol metabolism and endogenous aldehydes. These aldehyde compounds, such as 4-Hydroxynonenal (4-HNE) and 3,4-dihydroxyphenylacetaldehyde (DOPAL), are predominantly generated through lipid peroxidation and are known to form adducts with proteins, DNA, and lipids, thereby inducing neurotoxicity. Methods: This review examines the role of ALDH2 in central nervous system (CNS) diseases by analyzing epidemiological studies and disease models. The focus is on understanding the impact of the ALDH2 rs671 G>A polymorphism, which reduces or eliminates enzyme activity. Results: This genetic polymorphism of ALDH2 is closely associated with the onset of various central nervous system (CNS) diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD), schizophrenia, and stroke potentially linked to the accumulation of aldehyde compounds within the CNS. Conclusions: A deeper understanding of the mechanisms by which ALDH2 influences these diseases will enhance therapeutic strategies for patients carrying the ALDH2 rs671 polymorphism and also offer new insights for the prevention and diagnosis of these conditions.
Chen et al. (2024) studied this question.