Neurosteroids | Eva Kudová Group

About our group

Neurosteroids are endogenous steroids that are synthesized from cholesterol and produce rapid effects on neuronal excitability and synaptic function that involve direct or indirect modulation of neurotransmitter-gated ion channels, or other neurotransmitter receptors and transporters, rather than classic, nuclear hormone receptors. The effects of neurosteroids are mediated by interactions with ligand-gated ion channels such as glutamate, GABAA, glycine, nicotinic acetylcholine receptors, etc.

To find novel potentially beneficial drugs to treat neurological damage/neurodegeneration is one of the most investigated areas in contemporary pharmacology and neuroscience. Therefore, we design, synthesize and screen SMART Steroids – Steroidal Molecules As Rapid-acting Therapeutics. SMART steroids are neuroactive molecules, targeting primarily the N-Methyl-D-aspartate receptors (NMDARs) and show neuroprotective properties and minimal side effects in animal models of several neurological diseases like epilepsy, neuropathic pain, ischemia, neuropsychiatric disorders, and others.

Corticosteroids as Selective and Effective Modulators of Glycine Receptors

E. I. Solntseva J. V. Bukanova R. Kondratenko E. Kudová

ACS Chemical Neuroscience 14 (17): 3132–3142 (2023)

The mechanism of the negative impact of corticosteroids on the induction and progress of mental illness remains unclear. In this work, we studied the effects of corticosteroids on the activity of neuronal glycine receptors (GlyR) and GABA-A receptors (GABA_AR) by measuring the chloride current induced by the application of GABA (2 or 5 μM) to isolated cerebellar Purkinje cells (I_GABA) and by the application of glycine (100 μM) to pyramidal neurons of the rat hippocampus (I_Gly). It was found that corticosterone, 5α-dihydrodeoxycorticosterone, allotetrahydrocorticosterone, cortisol, and 17α,21-dihydroxypregnenolone were able to accelerate the desensitization of the IGly at physiological concentrations (IC₅₀ values varying from 0.39 to 0.72 μM). Next, cortisone, 11-deoxycortisol, 11-deoxycorticosterone, 5β-dihydrodeoxycorticosterone, and tetrahydrocorticosterone accelerated the desensitization of IGly with IC₅₀ values varying from 10.3 to 15.2 μM. Allotetrahydrocorticosterone and…

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Effects of Pregnanolone Glutamate and Its Metabolites on GABA_A and NMDA Receptors and Zebrafish Behavior

V. Abramová V. Leal Alvarado M. Hill T. Šmejkalová M. Malý K. Valeš I. Dittert P. Božíková B. Kysilov B. Hrčka Krausová V. Vyklický A. Balík M. Kořínek H. Chodounská E. Kudová D. Číž J. Martinovič J. Černý P. Bartůněk L. Vyklický

ACS Chemical Neuroscience 14 (10): 1870–1883 (2023)

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Novel neurosteroid pregnanolone pyroglutamate suppresses neurotoxicity syndrome induced by tetramethylenedisulfotetramine but is ineffective in a rodent model of infantile spasms

C. Chern M. Lauková A. Schonwald E. Kudová H. Chodounská C. J. Chern M. P. Shakarjian J. Velíšková L. Velíšek

Pharmacological Reports 75 (1): 177–188 (2023)

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Neurosteroids as positive and negative allosteric modulators of ligand-gated ion channels: P2X receptor perspective

S. Sivcev E. Kudová H. Zemková

Neuropharmacology 234: 109542 (2023)

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