논문 상세정보
Mimicking Neuroligin-2 Functions in β-Cells by Functionalized Nanoparticles as a Novel Approach for Antidiabetic Therapy
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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
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주제어
neuroligin-2 . Yb(III)-γ-Fe2O3 nanoparticles . INS-1E cells . insulin secretion . computer-aided drug design . bioactive peptides.
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- DOI : http://dx.doi.org/10.1021/acsami.6b10568
- American Chemical Society : 저널> 권호 > 논문
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