{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T22:46:34Z","timestamp":1777761994608,"version":"3.51.4"},"reference-count":100,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2022,11,26]],"date-time":"2022-11-26T00:00:00Z","timestamp":1669420800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2021YFA0719303"],"award-info":[{"award-number":["2021YFA0719303"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2022A1515010952"],"award-info":[{"award-number":["2022A1515010952"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["YYWT-0901-EXP-15"],"award-info":[{"award-number":["YYWT-0901-EXP-15"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003453","name":"Natural Science Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2021YFA0719303"],"award-info":[{"award-number":["2021YFA0719303"]}],"id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003453","name":"Natural Science Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2022A1515010952"],"award-info":[{"award-number":["2022A1515010952"]}],"id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003453","name":"Natural Science Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["YYWT-0901-EXP-15"],"award-info":[{"award-number":["YYWT-0901-EXP-15"]}],"id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"publisher"}]},{"name":"China Manned Space Flight Technology Project Chinese Space Station","award":["2021YFA0719303"],"award-info":[{"award-number":["2021YFA0719303"]}]},{"name":"China Manned Space Flight Technology Project Chinese Space Station","award":["2022A1515010952"],"award-info":[{"award-number":["2022A1515010952"]}]},{"name":"China Manned Space Flight Technology Project Chinese Space Station","award":["YYWT-0901-EXP-15"],"award-info":[{"award-number":["YYWT-0901-EXP-15"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Cranial radiation therapy is one of the most effective treatments for childhood brain cancers. Despite the ameliorated survival rate of juvenile patients, radiation exposure-induced brain neurogenic region injury could markedly impair patients\u2019 cognitive functions and even their quality of life. Determining the mechanism underlying neural stem cells (NSCs) response to irradiation stress is a crucial therapeutic strategy for cognitive impairment. The present study demonstrated that X-ray irradiation arrested NSCs\u2019 cell cycle and impacted cell differentiation. To further characterize irradiation-induced molecular alterations in NSCs, two-dimensional high-resolution mass spectrometry-based quantitative proteomics analyses were conducted to explore the mechanism underlying ionizing radiation\u2019s influence on stem cell differentiation. We observed that ionizing radiation suppressed intracellular protein transport, neuron projection development, etc., particularly in differentiated cells. Redox proteomics was performed for the quantification of cysteine thiol modifications in order to profile the oxidation-reduction status of proteins in stem cells that underwent ionizing radiation treatment. Via conjoint screening of protein expression abundance and redox status datasets, several significantly expressed and oxidized proteins were identified in differentiating NSCs subjected to X-ray irradiation. Among these proteins, succinate dehydrogenase [ubiquinone] flavoprotein subunit, mitochondrial (sdha) and the acyl carrier protein, mitochondrial (Ndufab1) were highly related to neurodegenerative diseases such as Parkinson\u2019s disease, Alzheimer\u2019s disease, and Huntington\u2019s disease, illustrating the dual-character of NSCs in cell differentiation: following exposure to ionizing radiation, the normal differentiation of NSCs was compromised, and the upregulated oxidized proteins implied a degenerative differentiation trajectory. These findings could be integrated into research on neurodegenerative diseases and future preventive strategies.<\/jats:p>","DOI":"10.3390\/biom12121759","type":"journal-article","created":{"date-parts":[[2022,11,28]],"date-time":"2022-11-28T03:28:49Z","timestamp":1669606129000},"page":"1759","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Radiotherapy Side Effects: Comprehensive Proteomic Study Unraveled Neural Stem Cell Degenerative Differentiation upon Ionizing Radiation"],"prefix":"10.3390","volume":"12","author":[{"given":"Dong","family":"Liang","sequence":"first","affiliation":[{"name":"Center for Energy Metabolism and Reproduction, Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meng","family":"Ning","sequence":"additional","affiliation":[{"name":"Center for Energy Metabolism and Reproduction, Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China"},{"name":"Department of Endocrinology, First Affiliated Hospital of Harbin Medical University, Harbin 150001, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hang","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Structural Heart Disease, The First Affiliated Hospital of Xi\u2019an Jiaotong University, Xi\u2019an 710061, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoyan","family":"He","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory of Molecular Imaging, School of Pharmacy, Shanghai University of Medicine & Health Sciences, Shanghai 201318, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6477-9055","authenticated-orcid":false,"given":"Peigen","family":"Ren","sequence":"additional","affiliation":[{"name":"Center for Energy Metabolism and Reproduction, Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8095-9008","authenticated-orcid":false,"given":"Xiaohua","family":"Lei","sequence":"additional","affiliation":[{"name":"Center for Energy Metabolism and Reproduction, Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuepei","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Bioorganic and Natural Products Chemistry, Center for Excellence in Molecular Synthesis, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"659","DOI":"10.3109\/02841869609083995","article-title":"Pathogenesis of irradiation-induced cognitive dysfunction","volume":"35","author":"Abayomi","year":"1996","journal-title":"Acta Oncol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2557","DOI":"10.1002\/cncr.21249","article-title":"Long-term outcomes of adult survivors of childhood cancer","volume":"104","author":"Robison","year":"2005","journal-title":"Cancer"},{"key":"ref_3","first-page":"4021","article-title":"Extreme sensitivity of adult neurogenesis to low doses of X-irradiation","volume":"63","author":"Mizumatsu","year":"2003","journal-title":"Cancer Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1285","DOI":"10.1212\/WNL.56.10.1285","article-title":"Adverse long-term effects of brain radiotherapy in adult low-grade glioma patients","volume":"56","author":"Vilkki","year":"2001","journal-title":"Neurology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1016\/S1470-2045(04)01507-4","article-title":"Late neurocognitive sequelae in survivors of brain tumours in childhood","volume":"5","author":"Mulhern","year":"2004","journal-title":"Lancet Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1006\/mcne.1996.0595","article-title":"The adult rat hippocampus contains primordial neural stem cells","volume":"8","author":"Palmer","year":"1997","journal-title":"Mol. 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