Mimicking Neuroligin-2 Functions in beta-Cells by Functionalized Nanoparticles as a Novel Approach for Antidiabetic Therapy

Both pancreatic beta-cell membranes and presynaptic active zones of neurons include in their structures similar protein complexes, which are respongible for mediating the secretion of bioactive molecules. In addition, these membrane-anchored proteins regulate interactions between neurons and guide the formation and maturation of synapses. These proteins include the neuroligins (e.g., NL-2) and their binding partners,, the neurexins. The insulin secretion and maturation of beta-cells is known to depend on their 3 dimensional (3D) arrangement.: It was also reported that both insulin secretion and the proliferation rates of beta-cells increase when cells are cocultured with clusters of NL-2. Use of full-length NL-2 or even its exocellular domain as potential beta-cell functional enhancers is limited by the biostabllity and bioavailability issues common to all protein-based therapeutics. Thus, based on molecular modeling approaches, a short peptide with the potential ability to bind neurexins was derived from the NL-2 sequence. Here, we show that the NL-2-derived peptide conjugates onto innovative functional maghemite (gamma-Fe2O3)-based nanoscale composite particles enhance beta-cell functions, in terms of glucose-stimulated insulin secretion and protect them under stress conditions. Recruiting the beta-cells' "neuron-like" secretory machinery as a target for diabetes treatment use has never been reported before. Such nanoscale composites might therefore provide a unique starting point for designing a novel class of antidiabetic therapeutic agents that possess a unique mechanism Of action.

Last Updated Date : 19/03/2018