Neuronal dendritic signaling complex (PSD)

Neuronal dendritic signaling complexes are specialized protein assemblies located at the postsynaptic membrane of neurons, primarily within dendritic spines (Sheng & Kim, 2011). These complexes, often referred to as the postsynaptic density (PSD), serve as the primary site for integrating chemical signals from neurotransmitters into intracellular biochemical cascades (Kennedy, 2000). They consist of a dense network of ionotropic receptors (such as NMDA and AMPA receptors), metabotropic receptors, scaffolding proteins like PSD-95, and various signaling enzymes including kinases and phosphatases (Kaizuka & Takumi, 2018). The structural and functional integrity of these complexes is essential for synaptic plasticity, which underlies learning and memory processes (Citri & Malenka, 2008). Dysregulation or disassembly of these complexes is implicated in a wide range of CNS disorders, including ischemic stroke, where excitotoxic signaling through the PSD-95/NMDA receptor link leads to neuronal death (Hill et al., 2020). Therapeutic interventions targeting these complexes include small molecules and peptides, such as nerinetide, designed to disrupt specific pathological protein-protein interactions or modulate receptor activity to restore normal synaptic function (Sun et al., 2018).

Other names

Postsynaptic densityPSDDendritic signalosomeSynaptic signaling complexPostsynaptic signaling complex

Inhibition of protein-protein interactions (PPI) within the postsynaptic density; modulation of ionotropic and metabotropic receptor signaling.