All in the family: Aldose
reductase and closely related aldo-keto reductases.
reductase, ocular diabetic complications and the development of topical Kinostat," Progress in Retinal and Eye Research, vol.
Gunn et al., "Discovery of 3 [(4,5,7-trifluorobenzothiazol-2-yl)methyl]indole-N-acetic acid (lidorestat) and congeners as highly potent and selective inhibitors of aldose
reductase for treatment of chronic diabetic complications," Journal of Medicinal Chemistry, vol.
Kinoshita, "Prevention of retinal vessel changes associated with diabetic retinopathy in galactose-fed dogs by aldose
reductase inhibitors," Archives of Ophthalmology, vol.
Retinal capillaries: Basement membrane thickening prevented with aldose
PKC-[delta] can be activated by aldose
reductase , and the PKC-[delta]/ p38aMAPK pathway can inhibit platelet-derived growth factor-mediated survival activity, resulting in the apoptosis of pericytes and the formation of acellular capillaries .
reductase, the metabolizing enzyme that catalyzes reduction of glucose to sorbitol, get up regulated in presence of high glucose concentration and produce more amount of Sorbitol (Muirhead and Hothersall, 1995).
Hyperglycemia significantly influences a protein complex that controls DNA transcription, cytokine production, and cell survival and activates NF-[kappa]B via an aldose
reductasecontrolled pathway .
In addition, it has been proposed that oxidative stress, advanced glycation end products (AGEs) formation, increased aldose
reductase activity, and activated protein kinase C (PKC) have been involved in the molecular mechanisms underlying neurodegeneration in T2DM [3, 4, 6, 7].
Recently, AG extract was reported to inhibit rat lens aldose
reductase and the formation of advanced glycation products .
Diabetic complications including neuropathy, nephropathy, cataracts, and retinopathy are considered to result from the accumulation of sorbitol, which is obtained from reduction of glucose by the catalytic activity of aldose
reductase (AR, EC 18.104.22.168) in the polyol pathway.
1: Reactions in the model containing AKR7A2 in the Gene-Protein-Reaction rules Reaction IDs are those from Recon 2 Reaction ID Reaction name ALR2 Aldose
reductase (methylglyosal) ALR3 Aldose
reductase (acetol) SBTR D-sorbitol reductase ARABR Arabinose reductase LALDO2x D-Lactaldehyde:NAD+ 1-oxidoreductase PPDOx Propane-1,2-diol:NAD+ 1-oxidoreductase Reaction ID GPR rule GPR rule (gene ID) ALR2 (8574.1) or (10327.1) or AKR7A2 or AKR1A1 or AKR1B1 (231.1) or (10327.2) ALR3 (8574.1) or (10327.1) or AKR7A2 or AKR1A1 or AKR1B1 (231.1) or (10327.2) SBTR (8574.1) or (10327.1) or AKR7A2 or AKR1A1 or AKR1B1 (231.1) or (10327.2) ARABR (8574.1) AKR7A2 LALDO2x (8574.1) AKR7A2 PPDOx (8574.1) AKR7A2 Tab.