NMDA-receptors (NMDARs) are a common downstream denominator for several neurodegenerative diseases, Alzheimer’s Diseases (AD) in particular, with the GluN2B-subtype being the primary culprit. Non-competitive NMDARs antagonists (FDA-approved memantine) may be used clinically to treat AD, but suffer from significant drawbacks such as lack of subunit- and cellular-specificity, leading to severe side-effects.
The research team is developing a novel treatment for neurodegeneration/AD consisting of short (~15 amino acid) modified peptides inspired by naturally occurring toxins. These modified peptides bind NMDAR-subunits non-competitively and inhibition the two main subunits found in the adult brain (GluN2A and -2B). One particular peptide varies from this family of peptides as it can both inhibit GluN2B and, remarkably, potentiate GluN2A. This duality shows its potential in reducing hyperexcitability and excitotoxity (afforded by inhibition of 2B) whilst promoting plasticity and cognitive enhancement (afforded by potentiating 2A).
- Reduced excitotoxicity
- Enhanced synaptic transmission and plasticity
- Specificity (with respect to cell population and receptor subtype)
Applications and Opportunities
- Treatment of neurodegeneration and related clinical symptoms
- Neurobiology research tools