Allele-specific rescue of neurexin behavioral phenotypes by monoamine-targeting compounds.

ABSTRACT: Neurexins are synaptic adhesion molecules associated with vast neurologic changes in humans, including neurodevelopmental delay, autism, schizophrenia, Tourette syndrome, and seizures. The NRXN1 gene produces >100 protein isoforms through alternative promoters and extensive splicing, which are differentially impacted by NRXN1 deletions found in patients. Yet pharmacologic targeting of NRXN1 isoforms or deletions has not been comprehensively studied. Here, we developed a behavioral screening approach in C. elegans to identify small molecule compounds that modify decreased activity levels caused by isoform-specific deletions of neurexin (nrx-1). Screening 190 compounds, we discovered that monoamine-targeting drugs differentially improve behavioral phenotype

SUBMITTER: Smisko WR 

PROVIDER: S-EPMC12889696 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature