Neurexin-3

Neurexin-3 (NRXN3) is a neuronal cell surface protein that mediates cell recognition and adhesion, and may participate in intracellular signaling (UniProt: Q9Y4C0). The protein is 1,643 amino acids long and functions at the synapse, where neurexins typically facilitate trans-synaptic interactions with neuroligin and other adhesion partners.

In human post-mortem Alzheimer's disease brain tissue, Neurexin-3 is consistently downregulated compared to age-matched controls (Chaparral AD proteomics). Quantitative proteomics using TMT labeling across four subcellular fractions (P2, P3, S2, S3) revealed a mean log2 fold-change of −0.61, indicating reduced protein abundance in AD tissue. This downregulation is observed across the measured fractions, suggesting a genuine decrease in Neurexin-3 levels rather than redistribution artifact.

Reduced neurexin expression may contribute to synaptic dysfunction and loss of adhesive interactions observed in Alzheimer's pathology, potentially underlying cognitive decline through impaired synaptic organization and trans-synaptic communication.