The aim of the project is to study the structure and molecular mechanisms of activation of ionotropic glutamate receptors (AMPA and NMDA subtypes), TRP channels and purinergic receptors. Glutamate receptors are an essential element of the excitatory signal transduction at synapses in the central nervous system. Transient receptor potential vanilloid 1 receptors (TRPV1) are expressed on both the peripheral and central branches of a subpopulation of DRG neurons and are considered to be the molecular integrators of noxious chemical and physical stimuli in the peripheral nerve endings.
Recently, the presynaptic TRPV1 receptors on the central branches of primary afferent neurons in the spinal cord were shown to have important role in nociceptive signaling, especially under pathological conditions. Purinergic receptors then play a role in the regulation of neuronal electrical activity, control of intracellular calcium signaling and also modulate the secretion of neurotransmitters and hormones. These membrane receptors are associated with the pathophysiological processes during the formation and development of higher neural functions disorders, neurodegenerative diseases (e.g. Alzheimer’s disease) or in chronic pain.
- Characterize the molecular mechanism(s) that control the activity of neurosteroids at NMDA receptors; and study synthetic analogs for their prospective effect to prevent excitotoxic neurodegeneration.
- Reveal the rules between neuronal activity, mRNA processing and receptor assembly of glutamate receptors.— Characterize the glutamate receptor complex gene variants presented in schizophrenia patients.
- Understand the effect of N-glycosylation on the regulation of NMDA receptors in neurons.
- Study the mechanisms of chronic pain and the role of nociceptive synaptic modulation in the spinal cord.
- Study purinergic signaling in the brain and the structure-function relationships of purinergic P2X receptors
Potential for Cooperation
We search for and test various compounds for their modulatory effect on the function of ion-channel receptors to improve the treatment of different neurological disorders. We are interested in cooperation directed especially towards understanding the mechanisms and treatment of neurodegenerative diseases and pain.