Review article

Discovery and development of NA-1 for the treatment of acute ischemic stroke

Authors: Beatrice BALLARIN1, Michael TYMIANSKI2
1 Institute of Medical Science, University of Toronto, Toronto, Ontario
2 Division of Neurosurgery, Institute of Medical Science Toronto Western Research Institute, University of Toronto, University Health Network 60 Leonard avenue, 8KD-406, Toronto, Ontario M5T 2R1, Canada
Corresponding to: Michael TYMIANSKI: Mike.Tymianski@uhn.ca,
DOI: 10.1038/aps.2018.5
Received: 27 November 2017
Accepted: 22 January 2018
Advance online: 22 March 2018

Abstract

Abstract
Stroke creates a complex interplay of multiple signaing pathways including excitotoxicity, ionic imbalance, inflammation, oxidative stress and apoptosis. There are very few treatments that have been shown to be beneficial in acute stroke. Recent findings have provided insights into the pathophysiology and mechanisms of ischemic stroke, complementing the traditional glutamate hypothesis: the molecular interaction between PSD95 and GluN2B has been identified as a culprit in stroke-mediated excitotoxicity, leading to the discovery of NA-1, a peptide that disrupts that interaction, as a potent neuroprotective agent for the treatment of acute stroke. In this review we describe its signaling cascade, the target of its therapeutic intervention and its translation from bench to clinical trial.
Keywords: ischemic stroke; PSD-95; GluN2B; protein-protein interaction; NA-1; Tat-NR2B9c