Zinc is a dynamic signaling element in the brain, critically contributing to sensory processing and synaptic plasticity. The zinc transporter ZnT3 packages it into synaptic vesicles of large populations of excitatory neurons throughout the brain. Zinc is thus co-released with glutamate during synaptic transmission, influencing the activity of the NMDA receptor. The Aizenman and Tzounopoulos laboratories described that another zinc transporter, namely ZnT1, by interacting with the NMDA receptor subunit GluN2A, strongly influence the actions of synaptically released zinc on the receptor.
Description
Researchers designed a cell and blood-brain-barrier permeable peptide termed TAT-N2AZ aimed at disrupting the ZnT1-GluN2A interaction. They observed that in the presence of the peptide, but not a control scramble, NMDA receptor activation was enhanced by decreasing the inhibitory actions of synaptically-released zinc. This is the first tool developed to enhance NMDA receptor function via a previous undescribed mechanism and may be useful in the treatment of disorders associated with NMDA receptor hypofunction, such as schizophrenia.
Applications
· Treating schizophrenia and other disorders associated with NMDA receptor hypofunction
Advantages
· Works via a previously unknown mechanism
Invention Readiness
In vitro data
IP Status
https://patents.google.com/patent/US20230034660A1
