Corticosteroid Action in the Brain: The Potential of Selective Receptor Modulation

Eva M.G. Viho, Jacobus C. Buurstede, Ahmed Mahfouz, Lisa L. Koorneef, Lisa T.C.M. Van Weert, René Houtman, Hazel J. Hunt, Jan Kroon, Onno C. Meijer

Research output: Contribution to journalArticleScientificpeer-review

8 Citations (Scopus)
31 Downloads (Pure)

Abstract

Glucocorticoid hormones have important effects on brain function in the context of acute and chronic stress. Many of these are mediated by the glucocorticoid receptor (GR). GR has transcriptional activity which is highly context-specific and differs between tissues and even between cell types. The outcome of GR-mediated transcription depends on the interactome of associated coregulators. Selective GR modulators (SGRMs) are a class of GR ligands that can be used to activate only a subset of GR-coregulator interactions, thereby giving the possibility to induce a unique combination of agonistic and antagonistic GR properties. We describe SGRM action in animal models of brain function and pathology, and argue for their utility as molecular filters, to characterize context-specific GR interactome and transcriptional activity that are responsible for particular glucocorticoid-driven effects in cognitive processes such as memory consolidation. The ultimate objective of this approach is to identify molecular processes that are responsible for adaptive and maladaptive effects of glucocorticoids in the brain.

Original languageEnglish
Pages (from-to)266-276
Number of pages11
JournalNeuroendocrinology
Volume109
Issue number3
DOIs
Publication statusPublished - 2019

Keywords

  • Glucocorticoid receptor
  • Learning and memory
  • Neurodegenerative diseases
  • Neuropsychiatric diseases
  • Nuclear receptor coregulators

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