NMDA receptor Serine tales: from physiology to physiopathology Event

Abstract: Glutamatergic transmission plays a pivotal role in synaptic physiology and brain activity. Amongst the ionotropic glutamate receptors, NMDARs play an exquisite finely tuned role, acting as coincident detectors of synaptic activity and determining further mechanisms of synaptic plasticity. However, under pathological conditions NMDARs dysfunction can induce synaptic dysfunction which can ultimately lead to brain pathological conditions. In the last years, our studies have been focused to understand the etiological role of NMDARs dysregulation in synaptopathies. The talk will be focused in our recent findings on the study of NMDARs dysregulation in syndromic and non-syndromic intellectual disability conditions. In the first part, we will explore the molecular etiology of Down syndrome (DS), a genetic condition caused by the trisomy of human chromosome 21, which is clinically associated with intellectual disability and an early onset of Alzheimer's disease. In this condition, we have detected important changes on the post-translational modification of the NMDARs that are associated with DS and explored novel therapeutic strategies. The second part of the talk will move to the study of non-syndromic intellectual disability caused by de novo mutations directly affecting the NMDARs. We will present our recent findings based on a multidisciplinary structure-function, and further translation to the clinical practice with beneficial effects.