In addition, GK-2 restored the level of the postsynaptic marker PSD-95, with the therapeutic effect amounting to 70% at the start of its administration after 6 h, and promoted restoration of the level of this marker at the start of administration 24 h after an experimental 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.
The nNOS-PSD-95 interaction is thus a potential target for functional restoration after stroke and ZL006, a small molecule inhibitor of this interaction, is a promising pharmacological lead compound.
The data suggest potential differential effects of PSD-95 inhibition in stroke and TBI that should be investigated further in future studies taking important experimental factors such as timing of treatment, dosage, and anesthesia into consideration.
Therapeutic effects of PSD-95 inhibition have been demonstrated in numerous studies of stroke; however only few studies have assessed the effects of PSD-95 inhibitors in traumatic brain injury (TBI).
Pharmacological inhibition of PSD-95 is a promising therapeutic strategy in the treatment of stroke, and positive effects of monomeric and dimeric PSD-95 inhibitors have been reported in numerous studies.