Aldehyde dehydrogenase family (ALDH)

The Aldehyde dehydrogenase (ALDH) family consists of 19 functional enzymes in humans that catalyze the NAD(P)+-dependent oxidation of aldehydes into carboxylic acids (Vasiliou et al., 2000, Pharmacogenetics). These enzymes are essential for the detoxification of reactive aldehydes generated during lipid peroxidation and the metabolism of alcohol (Jackson et al., 2011, Human Genomics). Beyond detoxification, ALDH members are involved in the biosynthesis of critical signaling molecules such as retinoic acid and neurotransmitters like GABA (NIH). ALDH2 is a primary target in alcohol use disorder, where its inhibition by drugs like disulfiram leads to the accumulation of acetaldehyde and a subsequent aversive reaction (Chen et al., 2014, Annual Review of Pharmacology and Toxicology). In the context of oncology, ALDH1A1 and other isoforms serve as markers for cancer stem cells and contribute to chemoresistance by inactivating drugs like cyclophosphamide (Tomita et al., 2016, Oncotarget). Emerging research also focuses on ALDH2 activators, such as Alda-1, which show potential in treating cardiovascular and neurodegenerative diseases by reducing toxic aldehyde levels (PubChem). Genetic polymorphisms, particularly the ALDH2*2 variant, significantly influence individual responses to alcohol and susceptibility to certain cancers (StatPearls). Overall, the ALDH family represents a versatile therapeutic target class with applications ranging from addiction medicine to precision oncology and cardioprotection.

Other names

Aldehyde dehydrogenaseALDH familyAldehyde:NAD+ oxidoreductaseALDHs

Drugs targeting the ALDH family primarily act through irreversible or reversible enzyme inhibition to treat alcohol dependence or overcome chemotherapy resistance, or through enzyme activation to enhance the detoxification of toxic aldehydes in cardiovascular and neurodegenerative conditions (Chen et al., 2014, Annual Review of Pharmacology and Toxicology; NIH).