In vitro pilot study of polydopamine nanoparticles as protective antioxidant agents on fibroblasts cells derived from ARSACS patients

ABSTRACT: Reactive oxygen species (ROS) are active molecules involved in several biological functions. When the production of ROS is not counterbalanced by the action of protective antioxidant mechanisms present in living organisms, a condition of oxidative stress can arise with consequent damage to biological structures. The brain is one of the main ROS-generating organs in the human body, with the consequence that most neurological disorders are associated with the overproduction of ROS. Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a neurodegenerative disease associated with mutations in the sacsin gene (SACS). At a cellular level, ARSACS is characterized by mitochondrial impairments, a reduction of bioenergetic processes, and by both an over-production of and an over sensitivity to ROS. Several antioxidant molecules have been proposed as a potential treatment for ARSACS, such as idebenone and resveratrol. Polydopamine nanoparticles (PDNPs) gained significant attention in recent years owing to their peculiar physic-chemical properties, and especially because of their antioxidant activity. PDNPs have shown a great ROS scavenging capacity that, combined with their completely organic nature that grants them the ability to be degraded and excreted by living organisms, make them a promising candidate in the treatment of oxidative stress-related disorders. In this work we assessed the effect of PDNPs upon human fibroblasts; in particular, we investigated the effects of PDNPs on populations of fibroblasts derived from healthy subjects and of fibroblasts derived from ARSACS patients, in terms of antioxidant properties and protein expression. PDNPs interaction with fibroblasts was analyzed in terms of biocompatibility, internalization and uptake pathway, reduction of ROS levels, prevention of ROS-induced apoptosis/necrosis, and protective action upon ROS-induced mitochondrial dysfunctions. Moreover, a complete proteomic analysis of the cells was performed to assess differences in terms of protein expression upon different treatments. Altogether, our data showed that PDNPs can partially counteract ROS-induced damages in both healthy and ARSACS patients-derived fibroblasts, making them a potential therapeutic candidate to treat or at least ameliorate the condition of oxidative stress associated with ARSACS disease.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

SUBMITTER: Martina Bartolucci  

LAB HEAD: Andrea Petretto

PROVIDER: PXD032916 | Pride | 2022-06-22

REPOSITORIES: Pride