Published online Jul 21, 2018. doi: 10.3748/wjg.v24.i27.2984
Peer-review started: April 12, 2018
First decision: May 21, 2018
Revised: June 28, 2018
Accepted: June 30, 2018
Article in press: June 30, 2018
Published online: July 21, 2018
Processing time: 98 Days and 21.8 Hours
Aldehyde dehydrogenase 2 (ALDH2) is best known for its critical detoxifying role in liver alcohol metabolism. However, ALDH2 dysfunction is also involved in a wide range of human pathophysiological situations and is associated with complications such as cardiovascular diseases, diabetes mellitus, neurodegenerative diseases and aging. A growing body of research has shown that ALDH2 provides important protection against oxidative stress and the subsequent loading of toxic aldehydes such as 4-hydroxy-2-nonenal and adducts that occur in human diseases, including ischemia reperfusion injury (IRI). There is increasing evidence of its role in IRI pathophysiology in organs such as heart, brain, small intestine and kidney; however, surprisingly few studies have been carried out in the liver, where ALDH2 is found in abundance. This study reviews the role of ALDH2 in modulating the pathways involved in the pathophysiology of IRI associated with oxidative stress, autophagy and apoptosis. Special emphasis is placed on the role of ALDH2 in different organs, on therapeutic “preconditioning” strategies, and on the use of ALDH2 agonists such as Alda-1, which may become a useful therapeutic tool for preventing the deleterious effects of IRI in organ transplantation.
Core tip: Aldehyde dehydrogenase 2 (ALDH2) plays a crucial role not only in liver ethanol metabolism but also in diverse pathophysiological dysfunctions including cardiovascular diseases, stroke, diabetes, neuro-degenerative dysfunctions, and aging. Its involvement has recently been identified in ischemia reperfusion injury (IRI). The present study provides an updated review of the literature on the role of ALDH2 in ischemia-reperfusion injury and its activation in different organs (heart, brain, kidney, intestine, etc) focusing especially on its possible use as a potential therapeutic target for preventing IRI associated with organ transplantation.