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Ubiquitin\u2010specific peptidase 25 (\n                    <jats:italic>USP25<\/jats:italic>\n                    ), a human chromosome 21 (HSA21) gene, encodes for a deubiquitinating enzyme overexpressed in DS patients. Dysregulation of USP25 has been associated with Alzheimer's phenotypes in DS, but its role in defective neurogenesis in DS has not been defined. In this study, we found that USP25 upregulation impaired cell cycle regulation during embryonic neurogenesis and cortical development. Overexpression of USP25 in hippocampus promoted the neural stem cells to glial cell fates and suppressed neuronal cell fate by altering the balance between cyclin D1 and cyclin D2, thus reducing neurogenesis in the hippocampus. USP25\u2010Tg mice showed increased anxiety\/depression\u2010like behaviors and learning and memory deficits. These results suggested that USP25 overexpression resulted in defective neurogenesis and cognitive impairments, which could contribute to the pathogenesis of DS. USP25 may be a potential pharmaceutical target for DS.\n                  <\/jats:p>","DOI":"10.1096\/fj.202300057r","type":"journal-article","created":{"date-parts":[[2023,5,12]],"date-time":"2023-05-12T10:03:56Z","timestamp":1683885836000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["USP25 contributes to defective neurogenesis and cognitive impairments"],"prefix":"10.1096","volume":"37","author":[{"given":"Fang","family":"Cai","sequence":"first","affiliation":[{"name":"Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Key Laboratory of Alzheimer's Disease of Zhejiang Province, Zhejiang Provincial Clinical Research Center for Mental Disorders Institute of Aging, School of Mental Health, Affiliated Kangning Hospital, The Second Affiliated Hospital, Yuying Children's Hospital, Wenzhou Medical University  Wenzhou Zhejiang China"},{"name":"Townsend Family Laboratories, 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The Second Affiliated Hospital, Yuying Children's Hospital, Wenzhou Medical University  Wenzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhao","family":"Wang","sequence":"additional","affiliation":[{"name":"Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Key Laboratory of Alzheimer's Disease of Zhejiang Province, Zhejiang Provincial Clinical Research Center for Mental Disorders Institute of Aging, School of Mental Health, Affiliated Kangning Hospital, The Second Affiliated Hospital, Yuying Children's Hospital, Wenzhou Medical University  Wenzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruixue","family":"Cao","sequence":"additional","affiliation":[{"name":"Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Key Laboratory of Alzheimer's Disease of Zhejiang Province, Zhejiang Provincial Clinical Research Center for Mental Disorders 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