NPP Seminar - Dr Hélène Marie, Molecular and Cellular Pharmacology Institute

Abstract: NMDA receptors (NMDARs) are essential actors in a large array of brain functions. Historically, they are described as ionotropic receptors, but there is also compelling evidence identifying an ion-flux independent signaling mode. Here, I will summarize our recent research providing compelling evidence that two fragments of the amyloid-b precursor protein (APP) are essential regulators of NMDAR function at excitatory synapses. I will highlight the importance of the C-terminal domain of APP in regulating the levels of the NMDAR GluN2B subunit at these synapses. I will also demonstrate that the recently identified APP fragment called AETA inhibits ionotropic signaling while promoting ion-flux independent NMDAR signaling. Beyond their well-known implication in Alzheimer’s disease, we thus argue that APP and its fragments are master regulators of NMDAR function in physiological conditions with potential implications in different NMDAR-linked disorders.

Academic Host: Prof Josef Kittler