{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T03:54:41Z","timestamp":1791431681114,"version":"4.3.3"},"reference-count":78,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2021,12,21]],"date-time":"2021-12-21T00:00:00Z","timestamp":1640044800000},"content-version":"vor","delay-in-days":354,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004096","name":"Kyushu University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004096","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["H25-ninchisho-ippann-004"],"award-info":[{"award-number":["H25-ninchisho-ippann-004"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003478","name":"Ministry of Health, Labour and Welfare","doi-asserted-by":"publisher","award":["H20-ninchisho-ippan-004"],"award-info":[{"award-number":["H20-ninchisho-ippan-004"]}],"id":[{"id":"10.13039\/501100003478","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["17H01391"],"award-info":[{"award-number":["17H01391"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["22221004"],"award-info":[{"award-number":["22221004"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Oxidative Medicine and Cellular Longevity"],"published-print":{"date-parts":[[2021,1]]},"abstract":"<jats:p>Oxidative stress is a major risk factor for Alzheimer\u2019s disease (AD), which is characterized by brain atrophy, amyloid plaques, neurofibrillary tangles, and loss of neurons. 8\u2010Oxoguanine, a major oxidatively generated nucleobase highly accumulated in the AD brain, is known to cause neurodegeneration. In mammalian cells, several enzymes play essential roles in minimizing the 8\u2010oxoguanine accumulation in DNA. MUTYH with adenine DNA glycosylase activity excises adenine inserted opposite 8\u2010oxoguanine in DNA. MUTYH is reported to actively contribute to the neurodegenerative process in Parkinson and Huntington diseases and some mouse models of neurodegenerative diseases by accelerating neuronal dysfunction and microgliosis under oxidative conditions; however, whether or not MUTYH is involved in AD pathogenesis remains unclear. In the present study, we examined the contribution of MUTYH to the AD pathogenesis. Using postmortem human brains, we showed that various types of <jats:italic>MUTYH<\/jats:italic> transcripts and proteins are expressed in most hippocampal neurons and glia in both non\u2010AD and AD brains. We further introduced MUTYH deficiency into <jats:italic>App<\/jats:italic><jats:sup>NL-G-F\/NL-G-F<\/jats:sup> knock\u2010in AD model mice, which produce humanized toxic amyloid\u2010<jats:italic>\u03b2<\/jats:italic> without the overexpression of APP protein, and investigated the effects of MUTYH deficiency on the behavior, pathology, gene expression, and neurogenesis. MUTYH deficiency improved memory impairment in <jats:italic>App<\/jats:italic><jats:sup>NL-G-F\/NL-G-F<\/jats:sup> mice, accompanied by reduced microgliosis. Gene expression profiling strongly suggested that MUTYH is involved in the microglial response pathways under AD pathology and contributes to the phagocytic activity of disease\u2010associated microglia. We also found that MUTYH deficiency ameliorates impaired neurogenesis in the hippocampus, thus improving memory impairment. In conclusion, we propose that MUTYH, which is expressed in the hippocampus of AD patients as well as non\u2010AD subjects, actively contributes to memory impairment by inducing microgliosis with poor neurogenesis in the preclinical AD phase and that MUTYH is a novel therapeutic target for AD, as its deficiency is highly beneficial for ameliorating AD pathogenesis.<\/jats:p>","DOI":"10.1155\/2021\/8635088","type":"journal-article","created":{"date-parts":[[2021,12,21]],"date-time":"2021-12-21T23:05:22Z","timestamp":1640127922000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["MUTYH Actively Contributes to Microglial Activation and Impaired Neurogenesis in the Pathogenesis of Alzheimer\u2019s Disease"],"prefix":"10.1155","volume":"2021","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0167-0391","authenticated-orcid":false,"given":"Yuri","family":"Mizuno","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0770-7079","authenticated-orcid":false,"given":"Nona","family":"Abolhassani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3515-6606","authenticated-orcid":false,"given":"Guianfranco","family":"Mazzei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8099-7087","authenticated-orcid":false,"given":"Kunihiko","family":"Sakumi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9659-9251","authenticated-orcid":false,"given":"Takashi","family":"Saito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1970-6903","authenticated-orcid":false,"given":"Takaomi C.","family":"Saido","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1345-9032","authenticated-orcid":false,"given":"Toshiharu","family":"Ninomiya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7826-870X","authenticated-orcid":false,"given":"Toru","family":"Iwaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2071-7861","authenticated-orcid":false,"given":"Ryo","family":"Yamasaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5307-2671","authenticated-orcid":false,"given":"Jun-ichi","family":"Kira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6739-242X","authenticated-orcid":false,"given":"Yusaku","family":"Nakabeppu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,12,21]]},"reference":[{"key":"e_1_2_10_1_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra0909142"},{"key":"e_1_2_10_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2012.11.007"},{"key":"e_1_2_10_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.arcmed.2012.11.003"},{"key":"e_1_2_10_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnen\/60.8.759"},{"key":"e_1_2_10_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2015.04.020"},{"key":"e_1_2_10_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.3780140"},{"key":"e_1_2_10_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mad.2011.08.003"},{"key":"e_1_2_10_8_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2005.03615.x"},{"key":"e_1_2_10_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.12444"},{"key":"e_1_2_10_10_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.1998.71052034.x"},{"key":"e_1_2_10_11_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.1997.68052061.x"},{"key":"e_1_2_10_12_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2005.03053.x"},{"key":"e_1_2_10_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.dnarep.2007.01.014"},{"key":"e_1_2_10_14_2","doi-asserted-by":"publisher","DOI":"10.1142\/9789814719735_0015"},{"key":"e_1_2_10_15_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-0-387-72974-9_3"},{"key":"e_1_2_10_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep04689"},{"key":"e_1_2_10_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)49494-5"},{"key":"e_1_2_10_18_2","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.10.5.1637"},{"key":"e_1_2_10_19_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/28.6.1355"},{"key":"e_1_2_10_20_2","doi-asserted-by":"publisher","DOI":"10.1007\/s004010100418"},{"key":"e_1_2_10_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2016.07.008"},{"key":"e_1_2_10_22_2","doi-asserted-by":"publisher","DOI":"10.1097\/00001756-200109170-00028"},{"key":"e_1_2_10_23_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-011-0484-4"},{"key":"e_1_2_10_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-84640-9"},{"key":"e_1_2_10_25_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI65053"},{"key":"e_1_2_10_26_2","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.87781"},{"key":"e_1_2_10_27_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21197170"},{"key":"e_1_2_10_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn.3697"},{"key":"e_1_2_10_29_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.41.4.479"},{"key":"e_1_2_10_30_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00308809"},{"key":"e_1_2_10_31_2","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bht101"},{"key":"e_1_2_10_32_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C300316200"},{"key":"e_1_2_10_33_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-06-4802"},{"key":"e_1_2_10_34_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-17999-3"},{"key":"e_1_2_10_35_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1235"},{"key":"e_1_2_10_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2005.06.030"},{"key":"e_1_2_10_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2007.06.002"},{"key":"e_1_2_10_38_2","doi-asserted-by":"publisher","DOI":"10.1006\/exnr.1999.7085"},{"key":"e_1_2_10_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2019.04.002"},{"key":"e_1_2_10_40_2","doi-asserted-by":"publisher","DOI":"10.1002\/cne.10945"},{"key":"e_1_2_10_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2015.08.022"},{"key":"e_1_2_10_42_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1349-7006.2011.01869.x"},{"key":"e_1_2_10_43_2","doi-asserted-by":"publisher","DOI":"10.1002\/humu.21343"},{"key":"e_1_2_10_44_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-59745-521-3_13"},{"key":"e_1_2_10_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nlm.2016.07.001"},{"key":"e_1_2_10_46_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4248-11.2012"},{"key":"e_1_2_10_47_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-017-0814-9"},{"key":"e_1_2_10_48_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11357-012-9507-6"},{"key":"e_1_2_10_49_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1800165115"},{"key":"e_1_2_10_50_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature21029"},{"key":"e_1_2_10_51_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.05.003"},{"key":"e_1_2_10_52_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.05.018"},{"key":"e_1_2_10_53_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainresbull.2020.01.003"},{"key":"e_1_2_10_54_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2015.11.054"},{"key":"e_1_2_10_55_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-006-0081-9"},{"key":"e_1_2_10_56_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkw170"},{"key":"e_1_2_10_57_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pnpbp.2017.07.010"},{"key":"e_1_2_10_58_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mad.2011.08.002"},{"key":"e_1_2_10_59_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkz912"},{"key":"e_1_2_10_60_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21051841"},{"key":"e_1_2_10_61_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2019.05.131"},{"key":"e_1_2_10_62_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2017.11.017"},{"key":"e_1_2_10_63_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2018.10.026"},{"key":"e_1_2_10_64_2","doi-asserted-by":"publisher","DOI":"10.1242\/dmm.040550"},{"key":"e_1_2_10_65_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12868-019-0496-6"},{"key":"e_1_2_10_66_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2017.09.006"},{"key":"e_1_2_10_67_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2015.12.001"},{"key":"e_1_2_10_68_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.dnarep.2019.102665"},{"key":"e_1_2_10_69_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1211103"},{"key":"e_1_2_10_70_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.25385"},{"key":"e_1_2_10_71_2","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.13062"},{"key":"e_1_2_10_72_2","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2013.00229"},{"key":"e_1_2_10_73_2","doi-asserted-by":"publisher","DOI":"10.4103\/1673-5374.272571"},{"key":"e_1_2_10_74_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2007.08.006"},{"key":"e_1_2_10_75_2","doi-asserted-by":"publisher","DOI":"10.1159\/000330363"},{"key":"e_1_2_10_76_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2017.10.021"},{"key":"e_1_2_10_77_2","doi-asserted-by":"publisher","DOI":"10.5306\/wjco.v11.i7.428"},{"key":"e_1_2_10_78_2","doi-asserted-by":"publisher","DOI":"10.1111\/acel.13429"}],"updated-by":[{"DOI":"10.1155\/2023\/9794081","type":"corrigendum","label":"Corrigendum","source":"publisher","updated":{"date-parts":[[2023,2,6]],"date-time":"2023-02-06T00:00:00Z","timestamp":1675641600000}}],"container-title":["Oxidative Medicine and Cellular Longevity"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/downloads.hindawi.com\/journals\/omcl\/2021\/8635088.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/downloads.hindawi.com\/journals\/omcl\/2021\/8635088.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1155\/2021\/8635088","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,7]],"date-time":"2024-08-07T18:45:15Z","timestamp":1723056315000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1155\/2021\/8635088"}},"subtitle":[],"editor":[{"given":"Zhao Zhong","family":"Chong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2021,1]]},"references-count":78,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,1]]}},"alternative-id":["10.1155\/2021\/8635088"],"URL":"https:\/\/doi.org\/10.1155\/2021\/8635088","archive":["Portico"],"relation":{"corrigendum":[{"id-type":"doi","id":"10.1155\/2023\/9794081","asserted-by":"object"}]},"ISSN":["1942-0900","1942-0994"],"issn-type":[{"value":"1942-0900","type":"print"},{"value":"1942-0994","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1]]},"assertion":[{"value":"2021-06-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-11-19","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-12-21","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"8635088"}}