Targeting PSD-95 as a Novel Approach in the Treatment of Stroke
| Autor: | Linda M. Haugaard-Kedström, Kristian Strømgaard, Eduardo Felipe Alves Fernandes |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Scaffold protein Synaptic cleft Chemistry Peptidomimetic PDZ domain Glutamate receptor Excitotoxicity medicine.disease_cause Cell biology 03 medical and health sciences 030104 developmental biology 0302 clinical medicine nervous system medicine NMDA receptor Ternary complex 030217 neurology & neurosurgery |
| Zdroj: | Springer Series in Translational Stroke Research ISBN: 9783319453446 |
| Popis: | During ischemia and stroke, a large excess of glutamate is released from the presynaptic terminal into the synaptic cleft. The NMDA receptor is activated by glutamate in the presence of glycine and triggers an influx of Ca2+ and hence induces excitotoxicity. PSD-95 is a scaffolding protein comprising three PDZ domains, one SH3 and one GK domain, which modulates numerous physiological relevant protein–protein interactions by interacting with the C-terminus or an internal binding motif of protein partners. The GluN2B subunit of the NMDA receptor and nNOS forms a ternary complex together with PSD-95 by interacting with PDZ1 and PDZ2 of PSD-95, respectively. Upon Ca2+ influx, this ternary complex induces the production of the toxic substance nitric oxide and further on ischemic brain damage. Numerous attempts and strategies have been applied to inhibit PSD-95/nNOS/NMDA receptor-induced excitotoxicity. Here we will present previous and ongoing efforts to develop and evaluate peptide, peptidomimetics and small molecule inhibitors targeting PSD-95. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|