Aldehyde dehydrogenase-2 as a therapeutic target

Introduction: Aldehyde dehydrogenase-2 (ALDH2) is a main contributor of the alcohol elimination process. Functional polymorphism in the ALDH2 gene and its inactive form causes unpleasant flushing responses after alcohol consumption and prevents excessive alcohol intake. ALDH2 plays a key role in removing endogenous aldehydes like 4-hydroxy-2-nonenal (4-HNE) and malondialdehyde (MDA) produced by lipid peroxidation triggered by oxidative stress. Additionally, ALDH2 is involved in the elimination of metabolites of neurotransmitters like 3,4-dihydroxyphenylacetaldehyde (DOPAL) and 3,4-dihydroxyphenylglycoaldehyde (DOPGAL) in the central nervous system (CNS).Areas covered: We examine the role of ALDH2 polymorphism in disease, aging and alcohol addiction and discuss its pharmacological targeting. Case-control studies indicate that the deficiency of ALDH2 activity influences the risk of numerous diseases while animal models show that ALDH2 activator Alda-1, could reduce cardiac ischemic damage. Moreover, many studies have reported the protective effect of Alda-1 against the development of neurodegenerative diseases. The literature search was conducted using PubMed and Cochrane Library up to August 2019.Expert opinion: ALDH2 is a promising therapeutic target in numerous diseases. The targeting of ALDH2 has much potential but requires further investigations and analysis to explore and establish its future potential role for the clinic.

4-HNE; ALDH2; Aldehyde dehydrogenase; DOPAL; alcohol use disorder; alda-1; coronary artery disease; ischemia/reperfusion injury.