PROtection MEdiated by Antioxidant NanoTEchnOlogy Against Neuronal Damage in Space 2 (PROMETEO 2, Nano Protection)

Oxidative stress (OS) is the mechanism at the base of many deleterious effects of spaceflight, involving exposure to microgravity (MG, also termed µg) and cosmic radiation (CR), and it is inherent to the genesis of several pathological conditions on Earth (among which Crohn’s and Parkinson’s diseases). Arising from the unbalanced production and elimination of pro-oxidant chemical species, OS implies short- and long-term alterations of targets from the molecular up to the whole organism level. The central nervous system (CNS) is the most critical target of OS, requiring special antioxidant protection with the increasing duration of spaceflights and in view of interplanetary travels. MG- and CR-induced cognitive and motor alterations, which are well known to progressively deteriorate human performance in space and can have life-threatening consequences on astronauts, can indeed be ascribed to dopamine dysregulation following OS generated during spaceflight. This project proposes the use of cerium oxide nanoparticles (nanoceria or NC, in space and on ground) and polydopamine-based nanoparticles (NP, on ground) to provide 1) antioxidant protection and 2) catecholaminergic support to neurons undergoing exposure to altered gravity and radiation. The focus is on neuronal cells involved in cognitive and motor functions both in space, where any behavioural impairments pose significant risks to manned expeditions, and on Earth, where dopaminergic neuron loss underlying Parkinson’s disease (PD) progression still requires effective contrast. This project in particular aims at exploring the connection between spaceflight and OS, by discriminating the effects of MG from those of CR, and at providing nanotechnology countermeasures to short- and potentially long-term alterations of the CNS due to spaceflight-induced reduction/oxidation (redox) reaction imbalance. This project also aspires at providing relevant evidence and therapeutic tools for the treatment of neurodegenerative conditions like PD on Earth.