Glucocorticoid receptors function in the pathophysiology of brain hypoxia

REVIEW ARTICLE

Glucocorticoid receptors function in the pathophysiology of brain hypoxia

Jan Gregrowicz 1 , Justyna Rogalska 2

1. Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, USA,
2. Department of Animal Physiology, Faculty of Biology and Environmental Protection, Nicolaus Copernicus University, Toruń, Poland,

Published: 2019-12-31
DOI: 10.5604/01.3001.0013.7193
GICID: 01.3001.0013.7193
Available language versions: en pl
Issue: Postepy Hig Med Dosw 2019; 73 : 838-849

 

Abstract

Glucocorticoid receptors are ligand-activated transcription factors, which play an important role in the brain, mainly in stress response regulation. There are two types of receptors for glucocorticosteroids: mineralocorticoid receptors (MR) with high-affinity for the ligands and glucocorticoid receptors (GR) with a tenfold lower affinity. Selective activation of the receptors during hypoxia may decide neuronal fate, especially in the hippocampus. Depending on the severity of hypoxia-induced damage, neurons undergo necrosis or apoptosis. In the penumbral region, where neurons die mainly through the process of apoptosis, selective GR activation increases excitotoxicity, interferes with apoptotic signalling pathways and causes energy deficit in the cells, all of which promote cell death. On the other hand, selective MR activation seems to be neuroprotective. It is suggested that the main role of MR in neuroprotection is to regulate the balance between anti- and proapoptotic proteins from bcl-2 family.

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