{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T17:31:18Z","timestamp":1779125478996,"version":"3.51.4"},"reference-count":42,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2025,6,15]],"date-time":"2025-06-15T00:00:00Z","timestamp":1749945600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Natural Science Foundation of China","award":["31570756"],"award-info":[{"award-number":["31570756"]}]},{"name":"National Natural Science Foundation of China","award":["32071222"],"award-info":[{"award-number":["32071222"]}]},{"name":"Special Funds for the Coconstruction Project of the Beijing Municipal Commission of Education","award":["31570756"],"award-info":[{"award-number":["31570756"]}]},{"name":"Special Funds for the Coconstruction Project of the Beijing Municipal Commission of Education","award":["32071222"],"award-info":[{"award-number":["32071222"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Tau pathology is one of the main pathological features of Alzheimer\u2019s disease (AD). Intracellular Tau may be released to the extracellular space upon neuron degeneration, where it has the potential to be toxic to other neurons. The propagation of Tau pathology, mediated by extracellular Tau aggregates, may underlie the pathogenesis of AD. Antibody therapies targeting Tau proteins are, therefore, considered highly promising. In this study, the cytotoxicity of extracellular Tau aggregates on SH-SY5Y cells was examined. The effect of extracellular Tau aggregates on intracellular Tau aggregation was also studied using a FRET-based assay. The extracellular Tau aggregates were found to cause intracellular Tau aggregation after entering the cells; meanwhile, ROS (reactive oxygen species) induced by Tau aggregates facilitated this process. A single-chain variable fragment antibody (scFv T1) inhibits Tau aggregation both extracellularly and intracellularly. ScFv T1 also inhibited the accumulation of ROS and alleviated the inflammation and apoptosis induced by Tau aggregates. These findings could provide experimental support for the study of neurotoxicity and related mechanisms of extracellular Tau aggregates, in addition to providing insights into the development of novel therapeutic agents to treat AD.<\/jats:p>","DOI":"10.3390\/biom15060872","type":"journal-article","created":{"date-parts":[[2025,6,16]],"date-time":"2025-06-16T14:03:11Z","timestamp":1750082591000},"page":"872","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["A Single-Chain Variable Fragment Antibody Alleviates Inflammation and Apoptosis of Neurons by Inhibiting Tau Aggregation"],"prefix":"10.3390","volume":"15","author":[{"given":"Zongbao","family":"Wang","sequence":"first","affiliation":[{"name":"Gene Engineering and Biotechnology Beijing Key Laboratory, National Demonstration Center for Experimental Life Sciences & Biotechnology Education, College of Life Sciences, Beijing Normal University, Beijing 100875, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingye","family":"Lin","sequence":"additional","affiliation":[{"name":"Gene Engineering and Biotechnology Beijing Key Laboratory, National Demonstration Center for Experimental Life Sciences & Biotechnology Education, College of Life Sciences, Beijing Normal University, Beijing 100875, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peipei","family":"Chang","sequence":"additional","affiliation":[{"name":"Gene Engineering and Biotechnology Beijing Key Laboratory, National Demonstration Center for Experimental Life Sciences & Biotechnology Education, College of Life Sciences, Beijing Normal University, Beijing 100875, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-2730-5650","authenticated-orcid":false,"given":"Mingzhu","family":"Sun","sequence":"additional","affiliation":[{"name":"Gene Engineering and Biotechnology Beijing Key Laboratory, National Demonstration Center for Experimental Life Sciences & Biotechnology Education, College of Life Sciences, Beijing Normal University, Beijing 100875, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sen","family":"Li","sequence":"additional","affiliation":[{"name":"Gene Engineering and Biotechnology Beijing Key Laboratory, National Demonstration Center for Experimental Life Sciences & Biotechnology Education, College of Life Sciences, Beijing Normal University, Beijing 100875, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3286","DOI":"10.1093\/brain\/awx243","article-title":"Tau pathology and neurodegeneration contribute to cognitive impairment in alzheimer\u2019s disease","volume":"140","author":"Bejanin","year":"2017","journal-title":"Brain"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1038\/nm.4443","article-title":"Amyloid-beta plaques enhance alzheimer\u2019s brain tau-seeded pathologies by facilitating neuritic plaque tau aggregation","volume":"24","author":"He","year":"2018","journal-title":"Nat. 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