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ACS applied materials & interfaces v.9 no.2, 2017년, pp.1189 - 1206   SCI SCIE
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Mimicking Neuroligin-2 Functions in β-Cells by Functionalized Nanoparticles as a Novel Approach for Antidiabetic Therapy

Munder, Anna (Department of Chemistry, Faculty of Exact Sciences, Bar-Ilan University, Ramat-Gan 52900, ); Israel, Liron L. (Department of Chemistry, Faculty of Exact Sciences, Bar-Ilan University, Ramat-Gan 52900, ); Kahremany, Shirin (Department of Chemistry, Faculty of Exact Sciences, Bar-Ilan University, Ramat-Gan 52900, ); Ben-Shabat-Binyamini, Rina (Department of Chemistry, Faculty of Exact Sciences, Bar-Ilan University, Ramat-Gan 52900, ); Zhang, Charles (Division of Endocrinology, Diabetes & Metabolism, Department of Medicine, University of California, Irvine, California 92697, ); Kolitz-Domb, Michal (Department of Chemistry, Faculty of Exact Sciences, Bar-Ilan University, Ramat-Gan 52900, ); Viskind, Olga (Department of Chemistry, Faculty of Exact Sciences, Bar-Ilan University, Ramat-Gan 52900, ); Levine, Anna (The Scientific Equipment Center, Faculty of Biological Sciences, Bar-Ilan University, Ramat-Gan 52900, ); Senderowitz, Hanoch (Department of Chemistry, Faculty of Exact Sciences, Bar-Ilan University, Ramat-Gan 52900, ); Chessler, Steven (Division of Endocrinology, Diabetes & Metabolism, Department of Medicine, University of California, Irvine, California 9269 ); Lellouche, Jean-Paul ( ); Gruzman, Arie ( );
  • 초록  

    Both pancreatic β-cell membranes and presynaptic active zones of neurons include in their structures similar protein complexes, which are responsible 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 β-cells is known to depend on their 3-dimensional (3D) arrangement. It was also reported that both insulin secretion and the proliferation rates of β-cells increase when cells are cocultured with clusters of NL-2. Use of full-length NL-2 or even its exocellular domain as potential β-cell functional enhancers is limited by the biostability 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 (γ-Fe 2 O 3 )-based nanoscale composite particles enhance β-cell functions in terms of glucose-stimulated insulin secretion and protect them under stress conditions. Recruiting the β-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. Graphic Abstract ACS Electronic Supporting Info


  • 주제어

    neuroligin-2 .   Yb(III)-γ-Fe2O3 nanoparticles .   INS-1E cells .   insulin secretion .   computer-aided drug design .   bioactive peptides.  

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