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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
Screening of novel 3α5β-neurosteroids for neuroprotective activity against glutamate- or NMDA-induced excitotoxicity
Screening of novel 3α5β-neurosteroids for neuroprotective activity against glutamate- or NMDA-induced excitotoxicity
Journal of Steroid Biochemistry and Molecular Biology 189: 195-203 (2019)
A broad variety of central nervous system diseases have been associated with glutamate induced excitotoxicity under pathological conditions. The neuroprotective effects of neurosteroids can combat this excitotoxicity. Herein, we have demonstrated the neuroprotective effect of novel steroidal N-methyl-D-aspartate receptor inhibitors against glutamate- or NMDA- induced excitotoxicity. Pretreatment with neurosteroids significantly reduced acute L-glutamic acid or NMDA excitotoxicity mediated by Ca2+ entry and consequent ROS (reactive oxygen species) release and caspase-3 activation. Compounds 6 (IC50 = 5.8 μM), 7 (IC50 = 12.2 μM), 9 (IC50 = 7.8 μM), 13 (IC50 = 1.1 μM) and 16 (IC50 = 8.2 μM) attenuated glutamate-induced Ca2+ entry more effectively than memantine (IC50 = 18.9 μM). Moreover, compound 13 shows comparable effect with MK-801 (IC50 = 1.2 μM) and also afforded significant protection without any adverse effect upon prolonged exposure. This drop in Ca2+ level resulted in…
Pregn-5-en-3β-ol and androst-5-en-3β-ol dicarboxylic acid esters as potential therapeutics for NMDA hypofunction: In vitro safety assessment and plasma stability
Steroids 147: 4-9 (2019)
Synthetic testosterone derivatives modulate rat P2X2 and P2X4 receptor channel gating
S. Sivčev
B. Slavíková
M. Rupert
M. Ivetic
M. Nekardová E. Kudová
H. Zemková
Journal of Neurochemistry 150 (1): 28-43 (2019)