{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T16:54:32Z","timestamp":1777395272123,"version":"3.51.4"},"reference-count":40,"publisher":"SAGE Publications","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAD"],"published-print":{"date-parts":[[2022,4,5]]},"abstract":"<jats:p>Background: Several recent findings have revealed that targeting of cell cycle reentry and (or) progression may provide an opportunity for the therapeutic intervention of Alzheimer\u2019s disease (AD). FOXG1 has been shown to play important roles in pattern formation, cell proliferation, and cell specification. Thus far, the roles of FoxG1 and its involvement in AD are largely unknown. Objective: Our study aimed to explore the intervention effect of FOXG1 on AD pathology and its potential mechanism with a particular focus on cell cycle regulation. Methods: We investigated the association of Foxg1 gene variants with AD-like behavioral deficits, p21 expression, neuronal apoptosis, and amyloid-\u03b2 (A\u03b2) aggregate formation; we further determined whether targeting FOXG1-regulated cell cycle has therapeutic potential in AD. Results: Paralleling AD-like behavioral abnormalities, neuronal apoptosis, and A\u03b2 deposits, a significant reduction in the expression of FOXG1 was observed in APP\/PS1 mice at 6 months of age. Using the APP\/PS1;Foxg1fl\/fl-CreAAV mouse line, we found that FOXG1 potentially antagonized cell cycle reentry by negatively regulating the levels of p21-activated kinase (PAK3). By reducing p21cip1-mediated arrest at the G2 stage and regulating cyclin A1- and cyclin B-dependent progression patterns of the cell cycle, FOXG1 blocked neuronal apoptosis and A\u03b2 deposition. Conclusion: These results indicate that FOXG1 contributes to the regulation of the neuronal cell cycle, thereby affecting brain abnormalities in AD. An elevation of the FOXG1 level, either pharmacologically or through other means, could present a therapeutic strategy for AD.<\/jats:p>","DOI":"10.3233\/jad-215144","type":"journal-article","created":{"date-parts":[[2022,2,15]],"date-time":"2022-02-15T13:27:02Z","timestamp":1644931622000},"page":"1255-1273","source":"Crossref","is-referenced-by-count":18,"title":["FOXG1 as a Potential Therapeutic Target for Alzheimer\u2019s Disease with a Particular Focus on Cell Cycle Regulation"],"prefix":"10.1177","volume":"86","author":[{"given":"Jia","family":"Wang","sequence":"first","affiliation":[{"name":"The Fourth Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu Province, China"},{"name":"School of Medicine, Jiangsu University, Zhenjiang, Jiangsu Province, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Si-Fei","family":"Ma","sequence":"additional","affiliation":[{"name":"School of Medicine, Jiangsu University, Zhenjiang, Jiangsu Province, China"},{"name":"Changzhou Blood Center, Changzhou, Jiangsu Province, PR China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qi","family":"Yun","sequence":"additional","affiliation":[{"name":"School of Medicine, Jiangsu University, Zhenjiang, Jiangsu Province, China"},{"name":"Changzhou Children\u2019s Hospital, Changzhou, Jiangsu Province, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wen-Jun","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Medicine, Jiangsu University, Zhenjiang, Jiangsu Province, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hong-Ru","family":"Zhai","sequence":"additional","affiliation":[{"name":"School of Medicine, Jiangsu University, Zhenjiang, Jiangsu Province, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hou-Zhen","family":"Shi","sequence":"additional","affiliation":[{"name":"School of Medicine, Jiangsu University, Zhenjiang, Jiangsu Province, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lan-Gui","family":"Xie","sequence":"additional","affiliation":[{"name":"School of Chemistry and Materials Science, Jiangsu Collaborative Innovation Center of Biomedical Functional Materials, Nanjing Normal University, Nanjing, Jiangsu Province, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jin-Jun","family":"Qian","sequence":"additional","affiliation":[{"name":"The Fourth Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu Province, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chun-Jie","family":"Zhao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Developmental Genes and Human Diseases, MOE, School of Medicine, Southeast University, Nanjing, Jiangsu Province, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei-Ning","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Medicine, Jiangsu 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