IOCB Prague

Eva Kudová Group

Neurosteroids
Targeted Research Group
CHEM cluster

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.


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Publications

All publications
Three neurosteroids as well as GABAergic drugs do not convert immediate postictal potentiation to depression in immature rats
Three neurosteroids as well as GABAergic drugs do not convert immediate postictal potentiation to depression in immature rats
Pharmacological Reports 72 (6): 1573–1578 (2020)
Background: Postictal potentiation presented immediately after cortical seizures in immature rats might be due to imbalance between excitation and inhibition. The aim of the present study was to determine whether augmentation of inhibition mediated by GABAA receptors could also suppress the postictal potentiation.Methods: Twelve-day old rats with implanted electrodes were used in our study. Five drugs were tested: the agonist muscimol, the positive modulator midazolam and three neurosteroids affecting GABAA receptors—allopregnanolone, pregnanolone sulphate and pregnanolone glutamate.Results: None of the five drugs was able to suppress potentiation appearing immediately after cortical epileptic afterdischarges, but all of them exhibited delayed anticonvulsant action 10 (in the case of midazolam and muscimol) or 20 min (all three steroids) after cortical seizures.Conclusion: Our results support a role of GABA in augmentation of cortical after discharges after longer intervals, whereas…
Lithocholic acid inhibits P2X2 and potentiates P2X4 receptor channel gating
Journal of Steroid Biochemistry and Molecular Biology 202: 105725 (2020)
3β-Isoobeticholic acid efficiently activates the farnesoid X receptor (FXR) due to its epimerization to 3α-epimer by hepatic metabolism
Journal of Steroid Biochemistry and Molecular Biology 202: 105702 (2020)
Synthetic structural modifications of neurosteroid pregnanolone sulfate: Assessment of neuroprotective effects in vivo
European Journal of Pharmacology 881: 173187 (2020)