• antioxidant
• arsacs
• blood-brain barrier
• mitochondria
• nanoparticles
• neurodegenerative
• oxidative stress
• polydopamine
• ros

The purpose of this work was to evaluate the therapeutic effect of antioxidant polydopamine nanoparticles (PDNPs) for the treatment of autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS), a neurodegenerative disorder attributed to a mutation of the gene responsible for the production of sacsin, a protein involved in mitochondrial network organization. The first part of the thesis was focused on the fabrication of PDNPs and their characterization in terms of morphology, hydrodynamic diameter, z-potential, and antioxidant activity. We tested PDNPs on different in vitro models like SH-SY5Y, hCMEC/D3, primary human astrocytes, and primary human fibroblasts, evaluating their effects on cell viability and internalization. We also assessed the ability of the nanoparticles to stimulate neurite outgrowth and neuronal differentiation. The ability of PDNPs to counteract reactive oxygen species (ROS) production upon pro-oxidative stimuli in different in vitro models was assessed through flow cytometry. Finally, PDNPs ability to prevent ROS induced damage upon mitochondria was evaluated in neuronal-like cells derived from differentiated SH-SY5Y, primary human fibroblasts from a healthy donor, and primary human fibroblasts from a patient affected by ARSACS.