Structural basis of glucocorticoid receptor signaling bias

Jeanneteau F(1), Meijer OC(2), Moisan MP(3).

Author information:
(1)Institut de génomique fonctionnelle, Université de Montpellier, INSERM, CNRS,
Montpellier, France.
(2)Leiden University Medical Center, Leiden, The Netherlands.
(3)Université de Bordeaux, INRAE, Bordeaux, France.

Dissociation between the healthy and toxic effects of cortisol, a major
stress-responding hormone has been a widely used strategy to develop
anti-inflammatory glucocorticoids with fewer side effects. Such strategy falls
short when treating brain disorders as timing and activity state within
large-scale neuronal networks determine the physiological and behavioral
specificity of cortisol response. Advances in structural molecular dynamics posit
the bases for engineering glucocorticoids with precision bias for select
downstream signaling pathways. Design of allosteric and/or cooperative control
for the glucocorticoid receptor could help promote the beneficial and reduce the
deleterious effects of cortisol on brain and behavior in disease conditions.

© 2022 British Society for Neuroendocrinology.

 

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