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Effect of Glucocorticoid and 11β-Hydroxysteroid-Dehydrogenase Type 1 (11β-HSD1) in Neurological and Psychiatric

Seetal Dodd1,2, David R Skvarc1,3, Olivia M Dean1,4

  • 1Deakin University, The Institute for Mental and Physical Health and Clinical Translation (IMPACT), School of Medicine, Barwon Health, Geelong, Australia.

The International Journal of Neuropsychopharmacology
|February 10, 2022
PubMed

Insights

11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) is a key enzyme in disease progression and a therapeutic target. Novel agents targeting 11β-HSD1 show potential for treating metabolic and neurological disorders, but more research is needed.

Area of Science:

  • Biochemistry
  • Pharmacology
  • Endocrinology

Background:

  • 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) plays a crucial role in regulating active cortisol levels.
  • Dysregulation of 11β-HSD1 is linked to various diseases, including metabolic syndrome, type 2 diabetes, and neurodegenerative disorders.
  • 11β-HSD1 is an attractive therapeutic target for managing these conditions.

Purpose of the Study:

  • To summarize the enzymatic mechanisms of 11β-HSD1.
  • To review novel therapeutic agents targeting 11β-HSD1.
  • To evaluate the potential of 11β-HSD1 modulators in disease management.

Main Methods:

  • Literature review of enzymatic mechanisms.
  • Analysis of preclinical and clinical studies on novel 11β-HSD1 inhibitors and activators.
  • Examination of evidence for symptom management in various disease models.

Main Results:

  • 11β-HSD1 modulators affect peripheral cortisol and cortisone levels.
  • Agents show promise in models of hypertension, type 2 diabetes, metabolic disorders, and Alzheimer's disease.
  • Evidence for clinical symptom management is mixed, with emerging data in psychiatric and neurological conditions.

Conclusions:

  • 11β-HSD1 is a significant therapeutic target with potential applications across multiple medical fields.
  • Novel agents modulating 11β-HSD1 activity warrant further investigation for their efficacy in disease treatment.
  • More research is required to establish the clinical utility of 11β-HSD1 modulators, particularly in psychiatry and neurology.
Keywords:
11β-HSD1 inhibitorsclinical translationglucocorticoidsneurologicalpsychiatric

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