title: Mimicking Neuroligin-2 Functions in β-Cells by Functionalized Nanoparticles as a Novel Approach for Antidiabetic Therapy.
abstract: 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-Fe2O3)-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.
authors.affiliation: Department of Chemistry, Faculty of Exact Sciences, Bar-Ilan University , Ramat-Gan 52900, Israel.
authors.forename: Anna
authors.initials: A
authors.lastname: Munder
authors.affiliation: Department of Chemistry, Faculty of Exact Sciences, Bar-Ilan University , Ramat-Gan 52900, Israel.|Nanomaterials Research Center, Institute of Nanotechnology & Advanced Materials (BINA), Bar-Ilan University , Ramat-Gan 52900, Israel.
authors.forename: Liron L
authors.initials: LL
authors.lastname: Israel
authors.affiliation: Department of Chemistry, Faculty of Exact Sciences, Bar-Ilan University , Ramat-Gan 52900, Israel.
authors.forename: Shirin
authors.initials: S
authors.lastname: Kahremany
authors.affiliation: Department of Chemistry, Faculty of Exact Sciences, Bar-Ilan University , Ramat-Gan 52900, Israel.|Nanomaterials Research Center, Institute of Nanotechnology & Advanced Materials (BINA), Bar-Ilan University , Ramat-Gan 52900, Israel.
authors.forename: Rina
authors.initials: R
authors.lastname: Ben-Shabat-Binyamini
authors.affiliation: Division of Endocrinology, Diabetes & Metabolism, Department of Medicine, University of California , Irvine, California 92697, United States.
authors.forename: Charles
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Chemistry, Faculty of Exact Sciences, Bar-Ilan University , Ramat-Gan 52900, Israel.|Nanomaterials Research Center, Institute of Nanotechnology & Advanced Materials (BINA), Bar-Ilan University , Ramat-Gan 52900, Israel.
authors.forename: Michal
authors.initials: M
authors.lastname: Kolitz-Domb
authors.affiliation: Department of Chemistry, Faculty of Exact Sciences, Bar-Ilan University , Ramat-Gan 52900, Israel.
authors.forename: Olga
authors.initials: O
authors.lastname: Viskind
authors.affiliation: The Scientific Equipment Center, Faculty of Biological Sciences, Bar-Ilan University , Ramat-Gan 52900, Israel.
authors.forename: Anna
authors.initials: A
authors.lastname: Levine
authors.affiliation: Department of Chemistry, Faculty of Exact Sciences, Bar-Ilan University , Ramat-Gan 52900, Israel.
authors.forename: Hanoch
authors.initials: H
authors.lastname: Senderowitz
authors.affiliation: Division of Endocrinology, Diabetes & Metabolism, Department of Medicine, University of California , Irvine, California 92697, United States.
authors.forename: Steven
authors.initials: S
authors.lastname: Chessler
authors.affiliation: Department of Chemistry, Faculty of Exact Sciences, Bar-Ilan University , Ramat-Gan 52900, Israel.|Nanomaterials Research Center, Institute of Nanotechnology & Advanced Materials (BINA), Bar-Ilan University , Ramat-Gan 52900, Israel.
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Lellouche
authors.affiliation: Department of Chemistry, Faculty of Exact Sciences, Bar-Ilan University , Ramat-Gan 52900, Israel.
authors.forename: Arie
authors.identifier: http://orcid.org/0000-0002-8006-4201
authors.initials: A
authors.lastname: Gruzman
mesh_terms: D000818:Animals; D015816:Cell Adhesion Molecules, Neuronal; D005290:Ferric Compounds; D007004:Hypoglycemic Agents; D007328:Insulin; D051379:Mice; D053758:Nanoparticles; D009419:Nerve Tissue Proteins
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; D005290:Ferric Compounds; D007004:Hypoglycemic Agents; D007328:Insulin; D009419:Nerve Tissue Proteins; C098003:neuroligin 2
keywords: INS-1E cells; Yb(III)-γ-Fe2O3 nanoparticles; bioactive peptides; computer-aided drug design; insulin secretion; neuroligin-2