Mimicking neuroligin‑2 functions in β‑cells by functionalized nanoparticles as a novel approach for antidiabetic therapy

Anna Munder, Liron L. Israel, Shirin Kahremany, Rina Ben-Shabat-Binyamini, Charles Zhang, Michal Kolitz-Domb, Olga Viskind, Anna Levine, Hanoch Senderowitz, Steven Chessler, Jean Paul Lellouche, Arie Gruzman

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

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.

Original languageEnglish
Pages (from-to)1189-1206
Number of pages18
JournalACS applied materials & interfaces
Volume9
Issue number2
DOIs
StatePublished - 18 Jan 2017

Bibliographical note

Publisher Copyright:
© 2017 American Chemical Society.

Keywords

  • Bioactive peptides
  • Computer-aided drug design
  • INS-1E cells
  • Insulin secretion
  • Neuroligin-2
  • Yb(III)-γ-Fe2O3 nanoparticles

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