Aldose reductase: New insights for an old enzyme

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Abstract

In the past years aldose reductase (AKR1B1; AR) is thought to be involved in the pathogenesis of secondary diabetic complications such as retinopathy, neuropathy, nephropathy and cataractogenesis. Subsequently, several AR inhibitors have been developed and tested for diabetic complications. Although these inhibitors have found to be safe for human use, they have not been successful in clinical studies because of limited efficacy. Recently, the potential physiological role of AR has been reassessed from a different point of view. Diverse groups suggested that AR, in addition to reducing glucose, also efficiently reduces oxidative stress-generated lipid peroxidation-derived aldehydes and their glutathione conjugates. Because lipid aldehydes alter cellular signals by regulating the activation of transcription factors such as NF-κB and AP1, inhibition of AR could inhibit such events. Indeed, a wide array of recent experimental evidence indicates that the inhibition of AR prevents oxidative stress-induced activation of NF-κB and AP1 signals that lead to cell death or growth. Furthermore, AR inhibitors have been shown to prevent inflammatory complications such as sepsis, asthma, colon cancer and uveitis in rodent animal models. The new experimental in vitro and in vivo data has provided a basis for investigating the clinical efficacy of AR inhibitors in preventing other inflammatory complications than diabetes. This review describes how recent studies have identified novel plethoric physiological and pathophysiological significance of AR in mediating inflammatory complications, and how the discovery of such new insights for this old enzyme could have considerable importance in envisioning potential new therapeutic strategies for the prevention or treatment of inflammatory diseases.

Original languageEnglish (US)
Pages (from-to)103-114
Number of pages12
JournalBiomolecular Concepts
Volume2
Issue number1-2
DOIs
StatePublished - Apr 1 2011

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Keywords

  • aldose reductase
  • cancer
  • diabetes
  • inflammation
  • oxidative stress
  • sepsis
  • uveitis

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Cellular and Molecular Neuroscience

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