{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T02:51:38Z","timestamp":1772160698546,"version":"3.50.1"},"reference-count":69,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2025,9,12]],"date-time":"2025-09-12T00:00:00Z","timestamp":1757635200000},"content-version":"vor","delay-in-days":11,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["22377027"],"award-info":[{"award-number":["22377027"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The abnormal generation and aggregation of A\u03b2 has been considered the central pathogenic mechanism of Alzheimer's disease (AD). Soluble A\u03b2 tends to aggregate into toxic oligomers, which initiate neuronal dysfunction. Therefore, attenuation of A\u03b2 oligomer formation might be an effective therapeutic strategy for AD. It has been reported that A\u03b2 can be nitrated at tyrosine 10. Our previous study found that nitration of Y10 in A\u03b2 significantly inhibits its aggregation and reduces its toxicity. However, the effects of A\u03b2 nitration on its neurotoxicity remain unclear. Here, we used SH\u2010SY5Y cells and a mouse model of AD induced by intrahippocampal A\u03b2\n                    <jats:sub>1\u201042<\/jats:sub>\n                    oligomer injection to investigate the effects of tyrosine nitration on the neurotoxicity of A\u03b2\n                    <jats:sub>1\u201042<\/jats:sub>\n                    . The results of dot blot, gel electrophoresis analysis, transmission electron microscopy, atomic force microscopy, and dynamic light scattering indicated that nitration of Y10 in A\u03b2\n                    <jats:sub>1\u201042<\/jats:sub>\n                    inhibits its oligomerization. A\u03b2\n                    <jats:sub>1\u201042<\/jats:sub>\n                    treatment perturbed the integrity of intracellular membranes, eventually leading to apoptosis of SH\u2010SY5Y cells. In contrast, nitrated A\u03b2\n                    <jats:sub>1\u201042<\/jats:sub>\n                    exhibited little neurotoxicity toward SH\u2010SY5Y cells. Additionally, mice injected with A\u03b2\n                    <jats:sub>1\u201042<\/jats:sub>\n                    oligomer developed cognitive impairment in behavioral tests. A\u03b2\n                    <jats:sub>1\u201042<\/jats:sub>\n                    oligomer caused neurotoxicity in the hippocampus of the mice, possibly through triggering apoptosis and neuroinflammation and promoting aberrant amyloid processing. As expected, nitrated A\u03b2\n                    <jats:sub>1\u201042<\/jats:sub>\n                    also had little effect on physiological and cognitive capacities. These results further confirm that nitration of Y10 in A\u03b2 can significantly inhibit its neurotoxicity. Moreover, our findings contribute to the understanding of the role of A\u03b2 in the development of AD.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                      <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc70218-gra-0001-m.png\">\n                        <jats:alt-text>image<\/jats:alt-text>\n                      <\/jats:graphic>\n                    <\/jats:boxed-text>\n                  <\/jats:p>","DOI":"10.1111\/jnc.70218","type":"journal-article","created":{"date-parts":[[2025,9,12]],"date-time":"2025-09-12T18:48:26Z","timestamp":1757702906000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Nitration of Tyrosine Residue\n                    <scp>Y10<\/scp>\n                    of A\u03b2\n                    <sub>1\u201042<\/sub>\n                    Ameliorates A\u03b2\n                    <sub>1\u201042<\/sub>\n                    \u2010Induced Neurotoxicity and Memory Impairment In\u00a0Vitro and In\u00a0Vivo"],"prefix":"10.1111","volume":"169","author":[{"given":"Jie","family":"Zhao","sequence":"first","affiliation":[{"name":"Key Laboratory of Novel Targets and Drug Study for Neural Repair of Zhejiang Province, School of Medicine Hangzhou City University  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Chen","sequence":"additional","affiliation":[{"name":"Key Laboratory of Novel Targets and Drug Study for Neural Repair of Zhejiang Province, School of Medicine Hangzhou City University  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Lu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Novel Targets and Drug Study for Neural Repair of Zhejiang Province, School of Medicine Hangzhou City University  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qihui","family":"Shi","sequence":"additional","affiliation":[{"name":"Shenzhen Key Laboratory of Marine Bioresource and Eco\u2010Environmental Sciences, College of Life Sciences and Oceanography Shenzhen University  Shenzhen China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qingyi","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Novel Targets and Drug Study for Neural Repair of Zhejiang Province, School of Medicine Hangzhou City University  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2544-2249","authenticated-orcid":false,"given":"Zhonghong","family":"Gao","sequence":"additional","affiliation":[{"name":"Hubei Key Laboratory of Bioinorganic Chemistry &amp; Materia Medica, School of Chemistry and Chemical Engineering Huazhong University of Science and Technology  Wuhan People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linghui","family":"Zeng","sequence":"additional","affiliation":[{"name":"Key Laboratory of Novel Targets and Drug Study for Neural Repair of Zhejiang Province, School of Medicine Hangzhou City University  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiong","family":"Liu","sequence":"additional","affiliation":[{"name":"Shenzhen Key Laboratory of Marine Bioresource and Eco\u2010Environmental Sciences, College of Life Sciences and Oceanography Shenzhen University  Shenzhen China"},{"name":"Shenzhen\u2010Hong Kong Institute of Brain Science\u2010Shenzhen Fundamental Research Institutions  Shenzhen China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,9,12]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1021\/pr900039c"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/jpi.12238"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00259-021-05253-y"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.21.12817"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2016.10.012"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1021\/acschemneuro.4c00284"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.719"},{"key":"e_1_2_10_9_1","article-title":"A11\u2010Positive \u03b2\u2010Amyloid Oligomer Preparation and Assessment Using Dot Blotting Analysis","volume":"135","author":"Chunhui H.","year":"2018","journal-title":"Journal of Visualized Experiments"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exger.2006.08.009"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2007.05.008"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0059113"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2014.04.001"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2022.109002"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2012.01.006"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrev.7b00568"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1159\/000100355"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-170819"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1039\/C3CP54839B"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/0197-0186(95)00067-I"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13311-014-0313-y"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1081-16.2016"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2022.120356"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2020.02.001"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1080\/17425247.2023.2228685"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2023.01.005"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-2010-1338"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-5728(89)90115-X"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1039\/C3CS60459D"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.5607\/en22004"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.24077"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-020-02196-w"},{"key":"e_1_2_10_33_1","article-title":"Intracerebroventricular Injection of Amyloid\u2010\u03b2 Peptides in Normal Mice to Acutely Induce Alzheimer\u2010Like Cognitive Deficits","volume":"109","author":"Kim H. 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