Development of a Method to Treat Alzheimer’s Disease by Protection of Synapses

NMDA receptors (NMDARs) are principal regulators of synaptic signaling in the brain. Modulation of NMDARs’ function and trafficking is important for the regulation of synaptic transmission and several forms of synaptic plasticity. Postsynaptic density protein 95 (PSD-95) acts as a scaffolding protein and stabilizes the surface and synaptic expression of NMDARs. NMDA receptors (NMDARs) are ionotropic glutamate receptors that are expressed throughout the nervous system and play crucial roles in neuronal development, synaptic plasticity, learning and memory. PSD-95 (Post Synaptic Density protein) or SAP90, a membrane-associated guanylate kinase (MAGUK), is the major scaffolding protein in the excitatory postsynaptic density (PSD) and a potent regulator of synaptic strength. It is almost exclusively located in the post synaptic density of neurons and is involved in anchoring synaptic proteins. Its direct and indirect binding partners include neuroligin, NMDA receptors, AMPA receptors, and potassium channels. Postsynaptic loss does not precede obvious Aβ (beta-amyloid or amyloid beta) and Tau deposition, but instead appears to occur as Aβ and Tau pathologies advance. This indicates that PSD-95 is an excellent intrinsic biomarker for post synaptic mechanisms and its expression is reduced in brain tissue from patients with Alzheimer’s Disease (AD) as well as in mouse models of AD. University of California, San Diego Office of Innovation and Commercialization licensing@ucsd.edu 858.534.5815