Xavier ALTAFAJ I TARDIO, IDIBELL, Spain

Xavier ALTAFAJ I TARDIO, invited by Michel Ronjat (Eq IIb)
Principal Investigator, IDIBELL - Neuropharmacology Unit, UB, Barcelona, Catalonia, Spain.
Website: iGluRs Lab ; Neuropharmacology Unit

Abstract

Glutamatergic transmission plays a pivotal role in synaptic physiology and brain activity. Amongst the ionotropic glutamate receptors, the NMDA receptor plays an exquisite tuned role, acting as coincident detector of synaptic activity and controlling synaptic plasticity. Concomitantly with its critical role, NMDAR dysfunction perturbs synaptic function and ultimately leads to neurological conditions associated with intellectual disability and hypotonia. The talk will shed light on the sensitivity of the glutamatergic neurotransmission system in two different neurological scenarios, namely Down syndrome (DS) and GRINpathies, a non-syndromic Paediatric Severe Encephalopathies associated with de novo mutations of GRIN genes encoding for NMDAR subunits. While resulting from different genetic etiologies, both conditions affect NMDAR structure, biochemistry, cell biology and biophysical properties, ultimately altering synaptic function. Importantly, the integration of in silico, in vitro and clinical findings is allowing to build-up a predictive algorithm towards a personalized medicine for NMDAR-related conditions, as supported by our pilot clinical trial on GRIN European children.