Supramolecular Nanostructure Activates TrkB Receptor Signaling of Neuronal Cells by Mimicking Brain-Derived Neurotrophic Factor

Brain-derived neurotrophic factor (BDNF), a neurotrophin that binds specifically to the tyrosine kinase B (TrkB) receptor, has been shown to promote neuronal differentiation, maturation, and synaptic plasticity in the central nervous system (CNS) during development or after injury and onset of disease. Unfortunately, native BDNF protein-based therapies have had little clinical success due to their suboptimal pharmacological properties. In the past 20 years, BDNF mimetic peptides have been designed with the purpose of activating certain cell pathways that mimic the functional activity of native BDNF, but the interaction of mimetic peptides with cells can be limited due to the conformational specificity required for receptor activation. We report here on the incorporation of a BDNF mimetic sequence into a supramolecular peptide amphiphile filamentous nanostructure capable of activating the BDNF receptor TrkB and downstream signaling in primary cortical neurons in vitro. Interestingly, we found that this BDN...