# Polydopamine‐Based Antioxidant Countermeasures Against Spaceflight‐Induced Neurodegeneration

## TL;DR

This study shows that polydopamine nanoparticles protect neurons from spaceflight-related stress, preserving their function and offering potential for both space missions and Earth-based neurodegenerative diseases.

## Contribution

The study demonstrates the neuroprotective efficacy of polydopamine nanoparticles in mitigating spaceflight-induced oxidative stress and transcriptional dysregulation.

## Key findings

- PDNPs stabilize antioxidant defense genes and mitochondrial function markers in space-stressed neurons.
- Transcriptomic analysis reveals PDNPs preserve neuronal homeostasis during microgravity and radiation exposure.
- Findings suggest PDNPs could serve as countermeasures for space-induced neurodegeneration and related Earth diseases.

## Abstract

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.

Polydopamine nanoparticles (PDNPs) protect neuron‐like cells from microgravity‐ and cosmic radiation‐induced oxidative stress. Through in‐flight and ground‐based experiments, it has been shown that PDNPs preserve neuronal and mitochondrial function, markedly mitigating transcriptional dysregulation caused by spaceflight. These findings highlight PDNPs as promising neuroprotective countermeasures for long‐duration missions.© 2026 WILEY‐VCH GmbH