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Radioprotection redefined: drug discovery at the intersection of tardigrade
biology and translational pharmacology
#MMPMID41341030
Cui Z
; Lin C
; Zhao H
; Wang X
Front Pharmacol
2025[]; 16
(?): 1713914
PMID41341030
show ga
Ionizing radiation inflicts lethal double-strand DNA breaks and oxidative stress
that underlie acute radiation syndrome, secondary malignancies, and dose-limiting
toxicity in radiotherapy; yet the conventional armamentarium of
radioprotectants-aminothiols, broad-spectrum antioxidants, cytokines, and
superoxide-dismutase mimetics-yields only modest benefit because of narrow
therapeutic windows, systemic toxicity, and inadequate protection of
radiosensitive tissues. In striking contrast, tardigrades (phylum Tardigrada)
routinely endure exposures beyond 5 kGy by deploying a multifaceted defense
repertoire that includes genome-shielding proteins such as damage suppressor
(Dsup) and Tardigrade DNA-Repair protein 1 (TDR1), families of intrinsically
disordered proteins that vitrify cytoplasm and scavenge radicals, antioxidant
pigments acquired via horizontal gene transfer, and exceptionally efficient
DNA-repair and redox networks. Viewing radioprotection through a translational
pharmacology lens reveals a pipeline of emerging modalities-including recombinant
or cell-penetrating proteins, mRNA therapeutics, peptidomimetics, and biomimetic
nanomaterials-while also spotlighting critical hurdles of scalable bioprocessing,
macromolecule stability, immunogenicity, and targeted delivery. By integrating
insights from extremophile biology with cutting-edge drug-discovery platforms,
tardigrade-inspired interventions promise to safeguard healthy tissue during
cancer treatment, reduce casualties in nuclear accidents, and shield astronauts
on deep-space missions, thereby redefining the future landscape of
radioprotection and transforming an evolutionary curiosity into a potent arsenal
of medical countermeasures.
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