Aldehyde dehydrogenase 3 family (ALDH3)

The Aldehyde dehydrogenase 3 (ALDH3) family is a group of enzymes responsible for the NAD(P)+-dependent oxidation of various endogenous and exogenous aldehydes into their corresponding carboxylic acids [1, 17]. This family includes four main members in humans: ALDH3A1, ALDH3A2, ALDH3B1, and ALDH3B2, which play critical roles in cellular detoxification and metabolic homeostasis [2, 14]. ALDH3A1 is highly expressed in the cornea and stomach, where it protects tissues from oxidative stress and UV radiation, but its overexpression in tumors is a major driver of resistance to oxazaphosphorine chemotherapeutics like cyclophosphamide [10, 11]. ALDH3A2, also known as fatty aldehyde dehydrogenase (FALDH), is essential for the metabolism of long-chain fatty aldehydes, and its genetic deficiency leads to Sjögren-Larsson syndrome, a neurocutaneous disorder [14, 16]. Therapeutic interest in the ALDH3 family focuses on developing selective inhibitors to sensitize cancer cells to treatment and exploring potential interventions for metabolic deficiencies [4, 11, 13]. These enzymes also serve as important biomarkers, with ALDH3A1 being a recognized marker for cancer stem cells in several solid tumors [8, 15].

Other names

ALDH3ALDHIIIAldehyde dehydrogenase family 3Dimeric NADP-preferring aldehyde dehydrogenaseFatty aldehyde dehydrogenaseFALDHALDH10ALDH3A1ALDH3A2ALDH3B1ALDH3B2

Inhibition of aldehyde dehydrogenase activity to prevent the detoxification of reactive aldehydes and chemotherapeutic metabolites, thereby increasing cellular sensitivity to oxidative stress and alkylating agents.