Dataset Information

Evaluation of Therapeutic Potential of Resveratrol-Loaded Nanostructured Lipid Carriers on Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay Patients Fibroblasts

ABSTRACT: Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a neurological disease characterized by autosomal recessive mutations in the sacsin gene (SACS), that cause in patients progressive cerebellar atrophy, damage of the peripheral nerves, and significant retinal changes and cognitive impairment. No effective therapies have been proposed for ARSACS, even if some evidences suggest that powerful antioxidant agents can be considered a therapeutic tool. Resveratrol (Res) is a natural polyphenol compound derived from vegetal sources, the application of which in biomedicine is increasing in the latest years because of its significant therapeutic effects, in particular in neurodegenerative diseases. In this study, we provide evidences about its potential exploitation in the treatment of ARSACS. Because of the low solubility of resveratrol in physiological media, a nanoplatform based on nanostructured lipid carriers is here proposed for its encapsulation and delivery. Resveratrol-loaded nanostructured lipid carriers (Res-NLCs) have been synthetized, characterized, and tested on healthy and ARSACS patient fibroblasts. Nanovectors displayed optimal stability and biocompatibility, and excellent antioxidant and anti-inflammatory activities. A comprehensive investigation at gene (with real-time quantitative RT-PCR (qRT-PCR)) and protein (with proteomics) level demonstrated the therapeutic potential of Res-NLCs, encouraging future investigations on pre-clinical models.

INSTRUMENT(S): Orbitrap Fusion ETD

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture, Skin, Fibroblast

DISEASE(S): Charlevoix-saguenay Spastic Ataxia

SUBMITTER: Martina Bartolucci

LAB HEAD: Martina Bartolucci

PROVIDER: PXD025718 | Pride | 2021-11-03

REPOSITORIES: Pride

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Source:

			Action	DRS
	ARSACS.zip	Other
	Ciofani_1120_Hela_180min_77.raw	Raw
	Ciofani_1120_Sen_CTR_1_78.raw	Raw
	Ciofani_1120_Sen_CTR_2_79.raw	Raw
	Ciofani_1120_Sen_CTR_3_80.raw	Raw

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Project description: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.

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Evaluation of Therapeutic Potential of Resveratrol-Loaded Nanostructured Lipid Carriers on Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay Patients Fibroblasts

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