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

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.