Exploring proteome perturbations by citicoline treament

This project deals with an investigation into perturbations of intracellular proteome of SH-SY5Y cells stimulated with two doses of citicoline (1 mM and 0.1 mM) for 6h and 18h in vitro. Citicoline is a nootropic agent used for the therapy of glaucoma, which is a neurodegenerative disorder characterized by degeneration of retinal ganglion cells and the optic nerve. Citicoline is an endogenous metabolite and synthetic precursor of phospholipids and neurotransmitters, thereby acting as a neuroenhancer. Over the last decade, several studies have pointed out neuroprotective activities of citicoline in different preclinical models. However, the molecular mechanisms underscoring citicoline neuroprotection have never been characterized yet. Herein, we set up an LFQ shot gun proteomic approach to address whether citicoline stimulation induces proteome alteration which could help explain its neuroprotective activities. The study strongly supports the hypothesis that citicoline treatment triggers a robust remodelling of intracellular proteome, potentiation the intracellular mechanisms deputed to proteostasis regulation, mitochondrial metabolism, together with transcription, mRNA splicing and protein translation. On the basis of these data, we propose that citicoline may promote proteostasis through processes referred to as hormesis.