Peer-reviewedCC BYCell Reports Physical Science
Selenium-engineered self-assembling protein nanoparticles rescue synaptic integrity and cognition via ferroptosis inhibition in Alzheimer’s mice
9 affiliations
- 1School of Life Science and Technology, Northwestern Polytechnical University, Youyi West Road 127, Xi’an, Shaanxi 710072, China
- 2School of Life Science and Technology, Northwestern Polytechnical University, Youyi West Road 127, Xi’an, Shaanxi 710072, China; Guangdong Provincial Key Laboratory for Plant Epigenetics, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen, Guangdong 518055, China
- 3Guangdong Provincial Key Laboratory for Plant Epigenetics, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen, Guangdong 518055, China
- 4School of Computer Science, Northwestern Polytechnical University, Youyi West Road 127, Xi’an, Shaanxi 710072, China
- 5Key Laboratory of Organosilicon Chemistry and Material Technology, Ministry of Education, College of Material, Chemistry and Chemical Engineering, Hangzhou Normal University, Hangzhou 311121, China
- 6School of Computer Science, Northwestern Polytechnical University, Youyi West Road 127, Xi’an, Shaanxi 710072, China; Corresponding author
- 7Key Laboratory of Organosilicon Chemistry and Material Technology, Ministry of Education, College of Material, Chemistry and Chemical Engineering, Hangzhou Normal University, Hangzhou 311121, China; Corresponding author
- 8Guangdong Provincial Key Laboratory for Plant Epigenetics, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen, Guangdong 518055, China; Corresponding author
- 9School of Biological Science and Medical Engineering, Southeast University, Nanjing, Jiangsu 210096, China; Corresponding author
Abstract
Alzheimer’s disease (AD) is the most common neurodegenerative disorder, yet effective disease-modifying therapies remain elusive. Here, we apply a semantic logic framework of Gene Ontology-based protein function prediction to identify ferroptosis-inhibitory proteins with potential neuroprotective activity. Guided by these predictions, we engineer selenium-modified apolipoprotein A1 supramolecular nanoparticles (Se-NDs) that intrinsically display glutathione peroxidase 4 (GPX4)-like catalytic activity and exhibit high brain penetrance. Se-ND suppresses lipid peroxidation, restores redox balance, and blocks ferroptotic neuronal death, thereby promoting mitochondrial repair and synaptic integrity and reversing structural and functional deficits underlying cognitive decline. Moreover, Se-ND synergizes with anti-inflammatory interventions and other AD-associated pathways. Our findings identify ferroptosis inhibition as a critical disease-modifying mechanism and establish Se-ND as a promising therapeutic avenue for Alzheimer’s disease.
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BibTeX
@article{shen2026seleniumengineered,
title = {{Selenium-engineered self-assembling protein nanoparticles rescue synaptic integrity and cognition via ferroptosis inhibition in Alzheimer’s mice}},
author = {Xin Shen and Jiantao Liu and Feiyuan Peng and Haile Zhao and Chunrui Qiao and Shaohua Shen and Yujie Li and Shafi Ullah and Airong Qian and Xiaoqi Wang and Xuequn Shang and Jiazuan Ni and Junqiu Liu and Xiubo Du and Yan Ge and Zhenhui Qi},
journal = {Cell Reports Physical Science},
year = {2026},
month = oct,
doi = {10.1016/j.xcrp.2026.103614},
url = {https://doi.org/10.1016/j.xcrp.2026.103614},
note = {CC BY},
}
RIS
TY - JOUR
TI - Selenium-engineered self-assembling protein nanoparticles rescue synaptic integrity and cognition via ferroptosis inhibition in Alzheimer’s mice
AU - Xin Shen
AU - Jiantao Liu
AU - Feiyuan Peng
AU - Haile Zhao
AU - Chunrui Qiao
AU - Shaohua Shen
AU - Yujie Li
AU - Shafi Ullah
AU - Airong Qian
AU - Xiaoqi Wang
AU - Xuequn Shang
AU - Jiazuan Ni
AU - Junqiu Liu
AU - Xiubo Du
AU - Yan Ge
AU - Zhenhui Qi
PY - 2026
DA - 2026/10/30
JO - Cell Reports Physical Science
DO - 10.1016/j.xcrp.2026.103614
UR - https://doi.org/10.1016/j.xcrp.2026.103614
AB - Alzheimer’s disease (AD) is the most common neurodegenerative disorder, yet effective disease-modifying therapies remain elusive. Here, we apply a semantic logic framework of Gene Ontology-based protein function prediction to identify ferroptosis-inhibitory proteins with potential neuroprotective activity. Guided by these predictions, we engineer selenium-modified apolipoprotein A1 supramolecular nanoparticles (Se-NDs) that intrinsically display glutathione peroxidase 4 (GPX4)-like catalytic activity and exhibit high brain penetrance. Se-ND suppresses lipid peroxidation, restores redox balance, and blocks ferroptotic neuronal death, thereby promoting mitochondrial repair and synaptic integrity and reversing structural and functional deficits underlying cognitive decline. Moreover, Se-ND synergizes with anti-inflammatory interventions and other AD-associated pathways. Our findings identify ferroptosis inhibition as a critical disease-modifying mechanism and establish Se-ND as a promising therapeutic avenue for Alzheimer’s disease.
SN - 2666-3864
ER -