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Effects of NMDA receptor modulators on cell death in models of excitotoxicity in vitro.
Strnadová, Lenka ; Smejkalová, Tereza (advisor) ; Skřenková, Kristýna (referee)
NMDA receptors are ionotropic glutamate receptors (iGluR) activated by the amino acid glutamate and mediating signal transmission in the central nervous system. Their proper activity is essential for synaptogenesis, neuronal plasticity and synaptic transmission. However, excessive activation of NMDAR causes strong influx of calcium ions into neurons which triggers several destructive effects, eventually ending with cell death. This so-called excitotoxicity is present not only in many neurodegenerative diseases, such as Alzheimer's disease or Parkinson's disease, but also in acute pathophysiological conditions, such as stroke or traumatic brain injury. General NMDAR inhibitors that could potentially prevent neuronal excitotoxicity have shown severe negative side effects in models in vivo. On the other hand, selective inhibitors of NMDA receptors with the ability to block the unwanted excessive activity while preserving NMDAR physiological function have shown to be therapeutically useful. This work is going to briefly summarize the knowledge of structure, activation and localization of NMDA receptors, then it is going to describe their rule in mediating neuronal toxicity and a few methods we can use to study excitotoxicity in vitro. Finally, this work will compare the effects of several known NMDAR...
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