Interazione dei recettori NMDA con le zattere lipidiche nei neuroni: il ruolo del colesterolo

NMDA receptors (NMDARs) are glutamate-gated ion channels that mediate excitatory neurotransmission in the central nervous system. NMDAR dysfunction may contribute to a variety of neurological and psychiatric conditions and detrimental effects can arise from either hyper- and hypoactivity. These receptors are localized in the post synaptic membrane in contact with lipid rafts (LRs). LRs are rich in glycolipids and in cholesterol and are associated with NMDARs through small proteins as caveolins and flotillins; these interactions are important to stabilize the membrane and to permit the correct function of the receptors. In accord to this, depletion or variations in the content of cholesterol and lipids cause a decrease of NMDAR responses and an increase in NMDAR desensitization. Moreover, dysfunctions in the interaction NMDARs/LRs and/or fragmentation of LRs cause an alteration of NMDAR-associated-LTP, leading to several possible neurological diseases as Alzheimer disease's (AD).