Leveraging Bioinformatics Approaches for Drug Repositioning in Space Radiation Protection
Thomas E. Diaz, Joseph A. Kerrigan Jr, Dawn E. Bowles, Yared H. Kidane
Abstract
The health effects of space radiation, primarily Galactic Cosmic Rays (GCRs), on humans remain largely unknown, with potential cardiovascular consequences posing a significant threat to astronauts on long-duration spaceflight missions. Currently, there are no established pharmacological countermeasures for GCR exposure. Drug repositioning offers a promising strategy to accelerate pharmaceutical research in space medicine. This study leverages existing bioinformatics techniques to identify and prioritize potential drug candidates associated with proteomic perturbations following simulated GCR exposure using previously published murine cardiac proteomic data.
Introduction
Space is an extreme environment that may pose unforeseen risks to the health and performance of those who undergo spaceflight. Of the few human studies conducted in space by the National Aeronautics and Space Administration (NASA) and its international counterparts, evidence of biological and physiological changes has been recorded. The etiology of these changes are largely unknown, however, there are a plethora of unique stressors that are proposed to be responsible. Some of these stressors include space radiation, isolation, distance from Earth, gravitational alterations, and harsh environments, among others.
Materials and Methods:
Heart tissue of 6-month-old, male C57BL/6 mice were collected approximately 8 months after exposure to GCR5-ion and compared to sham-irradiated mice. The methods of this collection process are described in detail in Bishawi et al, and this analysis builds on our groups’ previously published proteomics dataset. Differentially expressed proteins (DEPs) from mouse heart tissue were identified and organized with their corresponding gene names. Significance was defined as an adjusted p-value ≤ 0.05 and an absolute Log2 fold-change ≥ 0.263 (≥1.2-fold).
Discussion:
Radiation exposure is a well-known terrestrial risk factor for cardiovascular disease, primarily through accelerated atherosclerosis and chronic inflammation caused by the formation of reactive oxygen species (ROS) and reduced capacity to eliminate free radicals [28]. Although the components of GCR5-ion differ from those of radiation therapy, many of the biochemical responses to this stressor may be similar. Given the unethicality of radiation studies in humans, analog experiments using animal models serve as a valuable approach to bridging the gap in knowledge regarding the multi-omic effects of space radiation [29]. Several successful cases of drug repositioning have been documented using various approaches, including minoxidil for hair loss, sildenafil for erectile dysfunction, atomoxetine for attention-deficit/hyperactivity disorder, and fingolimod for multiple sclerosis, among others.
Citation: Diaz TE, Kerrigan Jr JA, Bowles DE, Kidane YH (2026) Leveraging bioinformatics approaches for drug repositioning in space radiation protection. PLoS One 21(9): e0357889. https://doi.org/10.1371/journal.pone.0357889
Editor: Mohammad Sadegh Taghizadeh, Shiraz University, IRAN, REPUBLIC OF ISLAMIC
Received: May 7, 2025; Accepted: August 24, 2026; Published: September 15, 2026.
Copyright: © 2026 Diaz et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Data Availability: All relevant data are within the manuscript and its Supporting Information files.
Funding: This work was supported by NASA research grant NNX16AK20G to DEB and NASA research grant NSSC22K0253 to DEB. The funders did not contribute to any aspect of this study.
Competing interests: The authors have declared that no competing interests exist.
