Pathophysiology of glycine transporters in glycinergic neurotransmission: hyperekplexia and pain

The group investigates glycinergic neurotransmission in health and different pathological scenarios such as hyperekplexia and pain. Hyperekplexia or startle disease (OMIM: 149400) is a rare neurological disorder, without specific treatment, characterized by pathological startle response to trivial stimuli that can be fatal in newborns. It is caused by the blockade of glycinergic inhibition by mutations in crucial synaptic proteins, such as the neuronal glycine transporter GlyT2. The aim is the search for personalized therapies for human hyperekplexia. To do this, pathogenic mechanisms of new GlyT2 variants in hyperekplexia patients are analyzed in terms of three-dimensional structure, intracellular traffic, interactome and interference in the development of glycinergic neurotransmission. Mechanisms of regulation and modulation of GlyT2 in pathological pain processes are also explored to obtain applicable information in analgesia.