Dataset Information

Proteomics and lipidomics analysis reveal lipid and calcium signalling as dysregulated pathways associated to sacsin loss

ABSTRACT: Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a rare uncurable neurodegenerative disease caused by mutation in SACS gene coding for sacsin, a large protein involved in protein homeostasis, mitochondrial function, cytoskeleton dynamics, autophagy, cell adhesion and vesicle trafficking. However, the pathogenetic mechanisms related to sacsin functions are still largely uncharacterized and therapies are lagging behind. To achieve further understanding in altered processes due to loss of sacsin, we used an untargeted proteomics approach in primary fibroblasts to compare protein profiles in ARSACS patients versus controls. Our analyses further confirmed an involvement of known biological pathways, also highlighting an implication of lipid component and calcium homeostasis in ARSACS.

INSTRUMENT(S): TripleTOF 5600

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Skin, Fibroblast

DISEASE(S): Charlevoix-saguenay Spastic Ataxia

SUBMITTER: Nicoletta Di Giorgi

LAB HEAD: Silvia Rocchiccioli

PROVIDER: PXD049199 | Pride | 2024-07-03

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	2019_12_20_Sacsin_Fib1_R1.wiff	Wiff
	2019_12_20_Sacsin_Fib1_R1.wiff.scan	Wiff
	2019_12_20_Sacsin_Fib1_R2.wiff	Wiff
	2019_12_20_Sacsin_Fib1_R2.wiff.scan	Wiff
	2019_12_20_Sacsin_Fib1_R3.wiff	Wiff

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Publications

Proteomics and lipidomic analysis reveal dysregulated pathways associated with loss of sacsin.

Galatolo Daniele D Rocchiccioli Silvia S Di Giorgi Nicoletta N Dal Canto Flavio F Signore Giovanni G Morani Federica F Ceccherini Elisa E Doccini Stefano S Santorelli Filippo Maria FM

Frontiers in neuroscience 20240607

<h4>Introduction</h4>Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a rare incurable neurodegenerative disease caused by mutations in the <i>SACS</i> gene, which codes for sacsin, a large protein involved in protein homeostasis, mitochondrial function, cytoskeletal dynamics, autophagy, cell adhesion and vesicle trafficking. However, the pathogenic mechanisms underlying sacsin dysfunction are still largely uncharacterized, and so attempts to develop therapies are still in t ...[more]

PMID: 38911600

Similar Datasets

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.