Aldehyde Dehydrogenases as Promising Targets for Treating ToxicAldehyde-related Diseases

Background: Mammals are exposed to various endogenous and exogenous aldehydes, and aldehyde dehydrogenases (ALDHs) function to metabolize these aldehydes into acids in order to counteract aldehyde over-load. ALDHs, therefore, play important roles in a series of physiological and pathophysiological processes. ALDHs activators and inhibitors are not only important probes for exploring ALDHs functions, but promising for the treatment of toxic aldehyde-related diseases. Methods: This review has comprehensively summarized the categories and characteristics of 19 human ALDHs, elaborated their related biological pathways, such as alcohol metabolism, retinoic acid (RA) production, neurotransmitter metabolism, etc. In addition, reported ALDHs activators and inhibitors have been summarized by listing their target, inhibition form, and clinical application. Results: On the one hand, summarization of the types and relative functions is useful for further research on aldehyde metabolic pathways and related diseases. On the other hand, a review of existing activators and inhibitors of ALDHs contributes to discovering new leading compounds and provides new insights. Conclusion: In consideration of the important role ALDH plays in toxic aldehyde-related diseases, ALDHs are promising targets for the treatment of toxic aldehyde-related diseases, and more research efforts are required to explore their pathophysiology and to develop new regulators.