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Paolo Cergna and Rosa Sapone (Altec) are gratefully acknowledged for the logistic support to the in-flight experiment. Astronaut Walter Villadei is also gratefully acknowledged for the care taken for experiment implementation aboard the ISS."},{"name":"DOI","value":"10.26030/n4wy-gy28"},{"name":"Data Source Accession","value":"GSE295652"},{"name":"Data Source Link","value":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE295652"},{"name":"Experiment Platform","value":"Kubik incubator"},{"name":"Flight Program","value":"International Space Station (ISS)"},{"name":"Funding","value":"This study was supported by Agenzia Spaziale Italiana (2021-2-R.1-2023)."},{"name":"Identifiers","value":""},{"name":"Managing NASA Center","value":""},{"name":"Mission End","value":"02/09/2024"},{"name":"Mission Link","value":"https://osdr.nasa.gov/bio/repo/data/missions/Ax-3"},{"name":"Mission Name","value":"Ax-3"},{"name":"Mission Start","value":"01/18/2024"},{"name":"Project Identifier","value":"PROMETEO II, Simulated_Microgravity"},{"name":"Project Link","value":""},{"name":"Project Title","value":""},{"name":"Project Type","value":"Spaceflight Study"},{"name":"Space Program","value":"Italian Space Agency (ASI)"},{"name":"Study Grant Number","value":""}],"description":"The spaceflight environment exposes biological systems to microgravity and cosmic radiation, which are factors known to induce oxidative stress and neurodegenerative processes. As the central nervous system is highly susceptible to disruptions in redox homeostasis, the development of effective strategies to safeguard astronaut health and cognitive function during extended space missions has become imperative. In this study, we investigate cerium oxide nanoparticles (nanoceria, NC) as an antioxidant agent for human neuron-like cells aboard the International Space Station. Nanoceria demonstrated excellent biocompatibility, strong antioxidant properties, and the ability to stimulate neurite extension under both Earth gravity and simulated microgravity. Following the return of the samples to Earth, transcriptomic analyses revealed that nanoceria effectively counteracted the detrimental transcriptional alterations triggered by spaceflight stressors, thereby maintaining neuronal homeostasis. Importantly, the expression of genes involved in antioxidant defense, mitochondrial activity, and dopamine metabolism remained stable in nanoceria-treated neurons, in contrast to the dysregulation observed in untreated controls. 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