{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T16:55:07Z","timestamp":1790268907655,"version":"4.1.0"},"reference-count":52,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2025,4,29]],"date-time":"2025-04-29T00:00:00Z","timestamp":1745884800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2025,5,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Strategies aimed at enhancing the capacity of neural stem cells (NSCs) to generate multipotential, proliferative, and migratory cell populations capable of efficient neuronal differentiation are crucial for structural repair following neurodegenerative damage. The role of Forkhead\u2010box gene 1 (FOXG1) in pattern formation, cell proliferation, and specification has been established. However, its involvement in Alzheimer's disease (AD) remains largely unknown. Here, we investigated the association between\n                    <jats:italic>Foxg1<\/jats:italic>\n                    gene variants and AD\u2010like behavioral deficits, amyloid\u2010\u03b2 (A\u03b2) aggregate formation, as well as p21 expression. Furthermore, we explored whether targeting the FOXG1\u2010regulated cell cycle contributes to the promotion of adult neurogenesis in the context of AD. In this study, we successfully induced overexpression of FOXG1 in the hippocampus of AD brains through adeno\u2010associated virus\u2010\n                    <jats:italic>Foxg1<\/jats:italic>\n                    infusion. Activation of FOXG1 rescued spatial learning disabilities, short\u2010term memory deficits, and sensorimotor gating impairments observed in AD transgenic animals. By inhibiting\n                    <jats:italic>p21<\/jats:italic>\n                    WAF1\/cyclin\u2010dependent kinase interacting protein 1 (\n                    <jats:italic>p21<\/jats:italic>\n                    <jats:sup>cip1\/waf1<\/jats:sup>\n                    )\u2010mediated cell cycle arrest, FOXG1 facilitates the activation and proliferation of NSCs. Additionally, the\n                    <jats:italic>Foxg1<\/jats:italic>\n                    gene promotes an increase in precursor population size and enhances neuroblast differentiation. These combined effects on proliferation and differentiation lead to the generation of postmitotic neurons within the hippocampus in AD animals. Together, these findings demonstrate the importance of cooperation between FOXG1 and p21 for maintaining NSC self\u2010renewal while facilitating neuronal lineage progression and contributing to endogenous neurogenesis during AD. Elevating levels of FOXG1 either pharmacologically or through alternative means could potentially serve as a therapeutic strategy for treating AD.\n                  <\/jats:p>","DOI":"10.1096\/fj.202403299rr","type":"journal-article","created":{"date-parts":[[2025,4,29]],"date-time":"2025-04-29T05:26:32Z","timestamp":1745904392000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["<scp>FOXG1<\/scp>\n                    Improves Cognitive Function in Alzheimer's Disease by Promoting Endogenous Neurogenesis"],"prefix":"10.1096","volume":"39","author":[{"given":"Wen","family":"Pan","sequence":"first","affiliation":[{"name":"The Fourth Affiliated Hospital of Jiangsu University  Zhenjiang Jiangsu People's Republic of China"},{"name":"Department of Laboratory Medicine, School of Medicine Jiangsu University  Zhenjiang Jiangsu People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Long\u2010Fei","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, School of Medicine Jiangsu University  Zhenjiang Jiangsu People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu\u2010Xin","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, School of Medicine Jiangsu University  Zhenjiang Jiangsu People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi\u2010Jie","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, School of Medicine Jiangsu University  Zhenjiang Jiangsu People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia\u2010Qing","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, School of Medicine Jiangsu University  Zhenjiang Jiangsu People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Qian","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, School of Medicine Jiangsu University  Zhenjiang Jiangsu People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng\u2010Zhi","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, School of Medicine Jiangsu University  Zhenjiang Jiangsu People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, School of Medicine Jiangsu University  Zhenjiang Jiangsu People's Republic of China"},{"name":"Zhenjiang Jieshengrui Biotechnology Co., Ltd  Zhenjiang Jiangsu People's Republic of 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