A genetically encoded secreted toxin potentiates synaptic NMDA receptors in hippocampal neurons and confers neuroprotection.

ABSTRACT: NMDA receptors (NMDARs) play essential roles in neuronal development, survival, and synaptic plasticity, to name a few. However, dysregulation in receptors' activity can lead to neuronal and synaptic damage, contributing to the development of various brain pathologies. Current pharmacological treatments targeting NMDARs remain limited, for instance due to insufficient receptor selectivity and poor spatial targeting. Genetic approaches hold promise to overcome some of these issues; however, require genetically encodable NMDAR-modulating peptides, which are scarce. Here, we explored NMDAR-selective peptide toxins from marine cone snails, which resulted in the necessary engineering of a posttranslational modification-free variant of Conantokin-P (naked Con-P). The naked form is

SUBMITTER: Carmi I 

PROVIDER: S-EPMC11826341 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature