Aldose Reductase

Aldose Reductase(ALR2) is a small, cytosolic, monomeric enzyme which belongs to the aldo-keto reductase superfamily. It catalyzes the NADPH dependent reduction of a wide variety of aldehydes to their corresponding alcohols, showing a broad substrate specificity and ALR2 is the key enzyme of the so called polyol pathway. Since its identification, in the early sixties, this enzyme has been always linked to the development of long term diabetic complications.It converts glucose to sorbitol, which is then oxidized to fructose by sorbitol dehydrogenase.In addition to the osmotic imbalance, an increase in the activity of the polyol pathway during hyperglycemia causes a substantial imbalance in the free cytosolic coenzyme ratios NADPH/NADP+ and NAD+/NADH, which contributes to the onset of hyperglycemic oxidative stress through the accumulation of reactive
oxygen species (ROS). ROS, in turn, trigger activation of downstream mechanisms, namely protein kinase C (PKC) isoforms, mitogen-activated protein kinases (MAPKs) and poly(ADP-ribose)polymerase (PARP), as well as the inflammatory cascade. ALR2 inhibition may be also considered a useful strategy to control pathological conditions emerging from tissue inflammation like atherosclerosis, sepsis, arthritis and also cancer. 


1.Quattrini L,et al. Expert Opin Ther Pat. 2019 Mar;29(3):199-213.