Decreasing excitotoxicity in Alzheimer’s disease by pharmacologically enhancing synaptic NMDAR content

Specific aim(s)/objective(s): Our goal is to validate the proof of principle that preventing the redistribution of NMDA Receptors from synaptic to extrasynaptic sites reduces the synaptic malfunction observed in Alzheimer’s disease (AD). To do so, we will utilize CX-4945, a Casein Kinase 2 (CK2) inhibitor that is currently in clinical phase 1/2 as a potential anti-tumoral. Specifically, we will evaluate the efficacy of CX-4945 in (Objective 1) controlling synaptic/extrasynaptic NMDAR balance and (Objective 2) reducing neuronal death. Then, we will investigate the impact of CX-4945 in AD by studying analyzing (Objective 3) apoptosis and (Objective 4) synapses loss in AD models.