IOCB Prague

Eva Kudová Group

Neurosteroids
Research Group
Junior
CHEM cluster

About our group

Our research is dedicated to discovering and designing novel neuroactive compounds that protect the brain and improve neurological function. We focus on developing safer, more effective treatments for conditions such as epilepsy, neuropathic pain, ischemia, and neuropsychiatric disorders, while also exploring broader applications such as reducing neuroinflammation, boosting cognitive performance, and slowing neurodegeneration linked to aging and disease.

A central theme of our work is neurosteroids – natural steroid molecules the brain produces from cholesterol. Acting within seconds to minutes, they rapidly alter neuronal circuit activity by modulating key receptor systems, including glutamate, GABAA, glycine, and nicotinic acetylcholine receptors. These fast, targeted actions allow neurosteroids to influence fundamental brain processes such as learning, memory, mood regulation, pain perception, and stress resilience.

We combine organic chemistry, molecular pharmacology, and neuroscience to explore these precise mechanisms and turn our insights into next-generation treatments that improve the quality of life for people living with complex neurological and psychiatric conditions.

In collaboration with the Second Faculty of Medicine at Charles University, we also run a joint laboratory integrating organic synthesis, molecular biology, and advanced neurofunctional imaging to enable selective modulation and visualization of neural processes for future diagnostics and therapies.

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Publications

All publications
Disease-associated nonsense and frame-shift variants resulting in the truncation of the GluN2A or GluN2B C-terminal domain decrease NMDAR surface expression and reduce potentiating effects of neurosteroids
Disease-associated nonsense and frame-shift variants resulting in the truncation of the GluN2A or GluN2B C-terminal domain decrease NMDAR surface expression and reduce potentiating effects of neurosteroids
Cellular and Molecular Life Sciences 81: 36 (2024)
N-methyl-D-aspartate receptors (NMDARs) play a critical role in normal brain function, and variants in genes encoding NMDAR subunits have been described in individuals with various neuropsychiatric disorders. We have used whole-cell patch-clamp electrophysiology, fluorescence microscopy and in-silico modeling to explore the functional consequences of disease-associated nonsense and frame-shift variants resulting in the truncation of GluN2A or GluN2B C-terminal domain (CTD). This study characterizes variant NMDARs and shows their reduced surface expression and synaptic localization, altered agonist affinity, increased desensitization, and reduced probability of channel opening. We also show that naturally occurring and synthetic steroids pregnenolone sulfate and epipregnanolone butanoic acid, respectively, enhance NMDAR function in a way that is dependent on the length of the truncated CTD and, further, is steroid-specific, GluN2A/B subunit-specific, and GluN1 splice variant-specific.…
Cholesterol metabolites modulate ionotropic P2X4 and P2X7 receptor current in microglia cells
Neuropharmacology 266: 110294 (2025)
A zuranolone nanocrystal formulation enables solubility-independent in vivo study of pentylenetetrazol-induced seizures in a rat model
RSC Pharmaceutics 1 (1): 37-46 (2024)
5β-reduced neuroactive steroids as modulators of growth and viability of postnatal neurons and glia
Journal of Steroid Biochemistry and Molecular Biology 239: 106464 (2024)