Polydopamine-Based Antioxidant Countermeasures Against Spaceflight-Induced Neurodegeneration.

Exposure to microgravity and cosmic radiation during spaceflight is responsible for oxidative stress onset, contributing to neuronal dysfunction and degeneration. The central nervous system is particularly vulnerable to redox imbalance and requires effective countermeasures to ensure astronaut health and performance on long-duration missions. In this study, the neuroprotective properties of polydopamine nanoparticles (PDNPs), known for their antioxidant activity, are investigated on neuron-like cells exposed to different gravitational and radiation regimes. Culture conditions included administration of PDNPs and permanence aboard the International Space Station (ISS) or on a random positioning machine. Transcriptomic analyses are conducted to assess gene expression alterations associated with oxidative stress, nuclear and mitochondrial integrity, and dopamine metabolism. In-flight, PDNP treatment mitigates the transcriptional changes induced by space stressors, preserving neuronal homeostasis. Notably, expression of key antioxidant defense genes, mitochondrial function markers and dopamine metabolism genes is stabilized in PDNP-treated neurons. This study provides preliminary evidence on the efficacy of PDNPs in protecting neuronal cells from the combined stressors associated with spaceflight: these findings suggest PDNPs as a promising countermeasure for space-induced neurodegeneration and support their potential translational application in the treatment of oxidative stress-related neurodegenerative pathologies on Earth.