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11beta-hydroxysteroid dehydrogenase type 1 as a novel therapeutic target in metabolic and neurodegenerative disease

Brian R Walker1, Jonathan R Seckl

  • 1University of Edinburgh, Endocrinology Unit, Western General Hospital, Edinburgh EH4 2XU, UK. B.Walker@ed.ac.uk

Expert Opinion on Therapeutic Targets
|December 4, 2003
PubMed

Insights

Inhibiting 11beta-hydroxysteroid dehydrogenase Type 1 (11HSD1) lowers tissue glucocorticoids, offering a new strategy for metabolic syndrome and cognitive aging. This approach shows promise without impacting stress hormone levels.

Area of Science:

  • Biochemistry
  • Endocrinology
  • Pharmacology

Background:

  • 11beta-hydroxysteroid dehydrogenase Type 1 (11HSD1) regenerates active glucocorticoids in tissues.
  • Elevated 11HSD1 activity is linked to obesity and metabolic syndrome.
  • Targeting 11HSD1 offers a tissue-specific approach to modulate glucocorticoid action.

Purpose of the Study:

  • To explore the therapeutic potential of inhibiting 11HSD1.
  • To evaluate the effects of 11HSD1 inhibition on metabolic syndrome features and cognitive function.
  • To establish the clinical priority for developing selective 11HSD1 inhibitors.

Main Methods:

  • Studies in transgenic mice models.
  • Administration of prototype 11HSD1 inhibitors in human subjects.
  • Assessment of metabolic parameters and cognitive function.

Main Results:

  • 11HSD1 inhibition demonstrated benefits in liver, adipose, and brain tissues.
  • Observed improvements in features of the metabolic syndrome.
  • Showed positive effects on cognitive dysfunction associated with aging.

Conclusions:

  • Inhibition of 11HSD1 is a promising therapeutic strategy.
  • Selective 11HSD1 inhibitors are a high priority for clinical development.
  • This approach offers a novel way to treat metabolic and cognitive disorders.

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