1 research outputs found
Mimicking Neuroligin‑2 Functions in β‑Cells by Functionalized Nanoparticles as a Novel Approach for Antidiabetic Therapy
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<sub>2</sub>O<sub>3</sub>)-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