Valentina Saverio

I earned my PhD in Medical Sciences and Biotechnology at the Cell Stress & Cell Death Lab (UPO, Dept. of Health Sciences, Novara). My work explored the molecular mechanisms underlying ferroptosis, a recently discovered non-apoptotic cell death pathway. My research investigated its role across various pathologies, including cancer (osteosarcoma, melanoma), autoimmune diseases (multiple sclerosis, celiac disease), and inflammatory bowel disease (IBD). My major discovery was the identification of a novel neuroprotective role for the Aldo-Keto Reductase (AKR) enzyme family in oligodendrocyte ferroptosis (see Redox Biology, 2024, 10.1016/j.redox.2024.103463). We demonstrated that the physiological and maturation-dependent increase in intracellular iron acts as a pro-ferroptotic signal, counteracted by AKR1C1 expression. Importantly, multiple sclerosis-related neuroinflammation downregulates AKR1C1 via miRNA-mediated mechanisms, heightening the susceptibility of mature oligodendrocytes to ferroptotic death.

Currently, I am a postdoctoral researcher at prof. Dmitry Lim’s Physiology Lab. My work aims to elucidate the role of astrocytic calcineurin (AstroCN) in the pathogenesis of Alzheimer’s disease (AD) and to develop a nanomedicine-based therapeutic strategy to target it. Calcineurin (CN), a Ca²⁺/calmodulin-dependent phosphatase, is highly expressed in astrocytes within amyloid-rich areas in AD brains. Its upregulation, driven by β-amyloid oligomers (AβOs), activates NFAT and NF-κB signalling pathways, promoting neuroinflammation, astrocytic dysfunction, and synaptic impairment.

Our recent findings show that selective depletion of AstroCN in pre-symptomatic 3xTg-AD mice prevents amyloid plaque formation, tau pathology, neuroinflammation, and cognitive decline. Building on this evidence, my current project (PNRR-MCNT2-2023-12377363, funded by the Italian Ministry of Health) combines engineered nanogels with the calcineurin inhibitor FK506 (FK-NGs) to selectively target AstroCN, offering a promising and innovative therapeutic approach against AD.