Autophagy-Induced Nanoparticle-Based Clearing of Toxic Huntingtin Protein Aggregates from Neuron Cells

Clearing of toxic huntingtin protein aggregates from neuron cells is critical for treatment of Huntington’s disease. However, this is very challenging and requires the control of intracellular processes and associated biochemical activities. Here, we report the designed nanoparticle-based clearing of toxic huntingtin protein aggregates via cellular autophagy induction. We have designed five different nanoparticles of 15–40 nm size that are composed of an iron oxide/zinc oxide/carbon core and a surface terminated with hemin/amine/arginine/trehalose. These nanoparticles induce cellular autophagy by three different mechanisms, and all of them clear toxic huntingtin aggregates from neuron cells. Such clearance of huntingtin aggregates by nanoparticles has shown a substantial increase in cell viability typically up to 7-fold. Our result suggests that autophagy-inducing nanodrugs may be designed for clearing toxic amyloid aggregates from the brain and treatment of neurodegenerative diseases.