Activation of TrkB receptors by NGFβ mimetic peptide conjugated polymersome nanoparticles

Activation of tyrosine kinase receptor B (TrkB), a neurotrophin receptor, has been shown to increase neuronal cell survival and promote regeneration. Stimulation of the TrkB receptor by neurotrophic growth factors has been identified as a possible therapeutic target for the treatment of neurodegenerative disorders. However, growth factor delivery is problematic because of a short half-life in vivo. We have conjugated hNgf-EE, a short peptide mimetic of NGFβ to the surface of polymersome nanoparticles and shown that they are capable of activating the TrkB receptor in vitro in the SHSY-G7 cell line. We propose that polymersomes could act as a scaffold for the delivery of TrkB activating moieties and that the polymersome size and polyethylene glycol surface have been shown to increase in vivo retention time. These multifunctional nanoparticles have potential for the treatment of neurodegenerative disorders by TrkB activation.From the Clinical EditorTyrosine kinase receptor B activation has been shown to promote regeneration and survival of neurons. However, growth factor delivery to stimulate these receptors remains problematic. The authors demonstrate that a peptide mimetic of NGFβ conjugated to the surface of polymersome nanoparticles is capable of activating the TrkB receptors. These nanoparticles may offer a novel treatment strategy for a variety of neurodegenerative disorders.

Graphical AbstractTrkB activation by hNgf EE conjugated polymersomes. The graphical abstract shows activation of TrkB receptors by polymesome supported hNgf EE peptides. Phosphorylation of TrkB receptors lead to stimulation of the MAPK/ERK, PLCγ and PI3K signaling pathway which promote cell survival.Figure optionsDownload high-quality image (192 K)Download as PowerPoint slide