{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,9]],"date-time":"2026-05-09T21:04:47Z","timestamp":1778360687360,"version":"3.51.4"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2022,7,11]],"date-time":"2022-07-11T00:00:00Z","timestamp":1657497600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"RIKEN Aging project"},{"name":"RIKEN Center for Brain Science"},{"name":"Agency for Medical Research and Development Brain Mapping by Integrated Neurotechnologies for Disease Studies","award":["JP18dm0207001"],"award-info":[{"award-number":["JP18dm0207001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,9,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Amyloid-\u03b2 and tau pathologies are important factors leading to neurodegeneration in Alzheimer\u2019s disease (AD); however, the molecular mechanisms that link these pathologies remain unclear. Assuming that important though as yet unidentified factors inhibit\/accelerate tau pathology and neuronal cell death under amyloid pathology, we sought to isolate and identify tau-interacting proteins from mouse brains with or without amyloid pathology. Among the proteins that were identified, we focused on protein arginine methyltransferase 8 (PRMT8), which interacts with tau specifically in the absence of amyloid pathology. To investigate the role of PRMT8 in the pathogenesis of AD, we conducted Prmt8 gene deletion and overexpression experiments in AppNL-G-F\/MAPT double knock-in mice and analysed the resulting pathological alterations. PRMT8-knockout did not alter the AD pathology in double knock-in mice, whereas PRMT8-overexpression promoted tau phosphorylation, neuroinflammation and vacuole degeneration. To evaluate if such a PRMT8-induced vacuole degeneration depends on tau pathology, PRMT8 was overexpressed in tau-KO mice, which were consequently found to exhibit vacuole degeneration. In addition, proteomic analyses showed that PRMT8 overexpression facilitated the arginine methylation of vimentin. Abnormal protein methylation could be involved in PRMT8-induced brain pathologies. Taken together, PRMT8 may play an important role in the formation of tau pathology and vacuole degeneration.<\/jats:p>","DOI":"10.1093\/jb\/mvac058","type":"journal-article","created":{"date-parts":[[2022,7,12]],"date-time":"2022-07-12T05:27:35Z","timestamp":1657603655000},"page":"233-243","source":"Crossref","is-referenced-by-count":11,"title":["Tau-binding protein PRMT8 facilitates vacuole degeneration in the brain"],"prefix":"10.1093","volume":"172","author":[{"given":"Ayano","family":"Ishii","sequence":"first","affiliation":[{"name":"RIKEN Center for Brain Science Laboratory for Proteolytic Neuroscience, , 2-1 Hirosawa, Wako City, Saitama 351-0198, Japan"},{"name":"Nippon Veterinary and Life Science University Laboratory of Comparative Medicine, , 1-7-1 Kyonancho, Musashino City, Tokyo 180-8602, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yukio","family":"Matsuba","sequence":"additional","affiliation":[{"name":"RIKEN Center for Brain Science Laboratory for Proteolytic Neuroscience, , 2-1 Hirosawa, Wako City, Saitama 351-0198, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naomi","family":"Mihira","sequence":"additional","affiliation":[{"name":"RIKEN Center for Brain Science Laboratory for Proteolytic Neuroscience, , 2-1 Hirosawa, Wako City, Saitama 351-0198, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naoko","family":"Kamano","sequence":"additional","affiliation":[{"name":"RIKEN Center for Brain Science Laboratory for Proteolytic Neuroscience, , 2-1 Hirosawa, Wako City, Saitama 351-0198, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takashi","family":"Saito","sequence":"additional","affiliation":[{"name":"RIKEN Center for Brain Science Laboratory for Proteolytic Neuroscience, , 2-1 Hirosawa, Wako City, Saitama 351-0198, Japan"},{"name":"Nagoya City University Graduate School of Medical Sciences Department of Neurocognitive Science, Institute of Brain Science, , 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, Aichi 467-8601, Japan"},{"name":"Nagoya University Department of Neuroscience and Pathobiology, Research Institute of Environmental Medicine, , Furo-cho, Chikusa-ku, Nagoya, Aichi 464-8601, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shin-ichi","family":"Muramatsu","sequence":"additional","affiliation":[{"name":"Jichi Medical University Division of Neurological Gene Therapy, , 3311-1 Yakushiji, Shimotsuke City, Tochigi 329-0498, Japan"},{"name":"The University of Tokyo Center for Gene and Cell Therapy, The Institute of Medical Science, , Tokyo 108-8639, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Makoto","family":"Yokosuka","sequence":"additional","affiliation":[{"name":"Nippon Veterinary and Life Science University Laboratory of Comparative Medicine, , 1-7-1 Kyonancho, Musashino City, Tokyo 180-8602, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takaomi C","family":"Saido","sequence":"additional","affiliation":[{"name":"RIKEN Center for Brain Science Laboratory for Proteolytic Neuroscience, , 2-1 Hirosawa, Wako City, Saitama 351-0198, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shoko","family":"Hashimoto","sequence":"additional","affiliation":[{"name":"RIKEN Center for Brain Science Laboratory for Proteolytic Neuroscience, , 2-1 Hirosawa, Wako City, Saitama 351-0198, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2022,7,11]]},"reference":[{"key":"2022100315384885800_ref1","doi-asserted-by":"crossref","first-page":"595","DOI":"10.15252\/emmm.201606210","article-title":"The amyloid hypothesis of Alzheimer\u2019s disease at 25\u00a0years","volume":"8","author":"Selkoe","year":"2016","journal-title":"EMBO Mol Med."},{"key":"2022100315384885800_ref2","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1186\/1750-1326-6-63","article-title":"Alzheimer\u2019s disease: synapses gone cold","volume":"6","author":"Koffie","year":"2011","journal-title":"Mol. 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