Aldehyde dehydrogenase 1A1 (ALDH1A1) and Aldehyde dehydrogenase 2 (ALDH2) (ALDH1A1/ALDH2)

Aldehyde dehydrogenase 1A1 (ALDH1A1) and Aldehyde dehydrogenase 2 (ALDH2) are critical members of the aldehyde dehydrogenase superfamily that catalyze the NAD+-dependent oxidation of aldehydes to their corresponding carboxylic acids [1, 7]. ALDH1A1 is a cytosolic enzyme primarily involved in retinoic acid biosynthesis and is a well-established marker for cancer stem cells, where it contributes to drug resistance by detoxifying chemotherapeutic agents like cyclophosphamide [2, 3, 9]. ALDH2 is a mitochondrial enzyme and the primary catalyst for the detoxification of ethanol-derived acetaldehyde and reactive aldehydes produced during oxidative stress, such as 4-hydroxy-2-nonenal (4-HNE) [1, 5, 14]. Both enzymes are significant therapeutic targets; their inhibition by drugs like disulfiram is utilized in the treatment of alcohol use disorder and is being explored to sensitize tumors to chemotherapy [7, 11]. Conversely, the activation of ALDH2 using small molecules like Alda-1 is a potential strategy for treating cardiovascular and neurodegenerative diseases by enhancing the clearance of toxic aldehydes [1, 4, 5]. Genetic polymorphisms, particularly the ALDH2*2 variant (rs671), significantly impact enzyme activity and are associated with altered disease risks and drug responses [6, 14].

Other names

Retinaldehyde dehydrogenase 1RALDH1Mitochondrial aldehyde dehydrogenaseALDH-E2ALDH1ALDCPQR3

Inhibition of enzymatic activity through covalent or non-covalent binding to the active site, preventing the oxidation of aldehydes; or activation of the enzyme to enhance detoxification of reactive aldehydes [7, 12].