Aim
The human-immunodeficiency virus (HIV) envelope protein gp120 promotes synaptic damage similar to that observed in people living with HIV who have neurocognitive disorders. The neurotoxic effect of gp120 appears to occur through the α-helix motif that binds to neuronal microtubules (MTs). In this study, we examined the ability of short peptide derivatives from Helix-A, a peptide synthesized based on α-helix structure of gp120, to displace gp120 from binding to MTs and prevent its neurotoxic effects.
Methods
Surface plasmon resonance was used to determine the binding of Helix-A and its modifications to MTs. Helix-A peptide and derivatives were delivered inside rat primary cortical neurons by mesoporous silica nanoparticles (MSN). Neuronal processes and survival were evaluated by microtubule associated protein 2-immunostaining and Hoechst/Propidium iodide, respectively.
Results
Surface plasmon resonance analysis revealed that Helix-A but not its modifications binds to MTs. Also, only Helix-A MSN but not other peptides prevented the ability of gp120 to reduce neuronal processes as well as neuronal survival. Thus, the amino acid structure of Helix-A is key for its neuroprotective activity.