{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,20]],"date-time":"2025-02-20T05:14:56Z","timestamp":1740028496903,"version":"3.37.3"},"reference-count":0,"publisher":"IOS Press","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2011]]},"abstract":"<jats:p>Cell cycle proteins are elevated in the brain of patients and in transgenic models of Alzheimer's disease (AD), suggesting that aberrant cell cycle re-entry plays a key role in this disorder. However, the precise relationship between cell cycle reactivation and the AD hallmarks, amyloid-beta (A&amp;beta;) plaques and tau-laden neurofibrillary tangles, remains unclear. We sought to determine whether cell cycle reactivation initiates in direct response to A&amp;beta; and tau accumulation or whether it occurs as a downstream consequence of neuronal death pathways. Therefore, we used a triple transgenic mouse model of AD (3xTg-AD) that develops plaques and tangles, but does not exhibit extensive neuronal loss, whereas to model hippocampal neuronal death a tetracycline-regulatable transgenic model of neuronal ablation (CaM\/Tet-DTAmice) was used. Cell-cycle proteins activation was determined in these two models of neurodegeneration, using biochemical and histological approaches. Our findings indicate that Cdk4, PCNA and phospho-Rb are significantly elevated in CaM\/Tet-DTAmice following neuronal death. In contrast, no significant activation of cell-cycle proteins occurs in 3xTg-AD mice versus non-transgenic controls. Taken together, our data indicate that neuronal cell cycle reactivation is not a prominent feature induced by A&amp;szlig; or tau pathology, but rather appears to be triggered by acute neuronal loss.<\/jats:p>","DOI":"10.3233\/978-1-60750-733-8-139","type":"book-chapter","created":{"date-parts":[[2025,2,19]],"date-time":"2025-02-19T13:48:12Z","timestamp":1739972892000},"source":"Crossref","is-referenced-by-count":0,"title":["Activation of Cell Cycle Proteins in Transgenic Mice in Response to Neuronal Loss But Not A&amp;szlig; and Tau Pathology"],"prefix":"10.3233","author":[{"family":"Lopes Joao P.","sequence":"additional","affiliation":[]},{"family":"Blurton-Jones Mathew","sequence":"additional","affiliation":[]},{"family":"Yamasaki Tritia R.","sequence":"additional","affiliation":[]},{"family":"Agostinho Paula","sequence":"additional","affiliation":[]},{"family":"LaFerla Frank M.","sequence":"additional","affiliation":[]}],"member":"7437","container-title":["Advances in Alzheimer\u2019s Disease","Handbook of Animal Models in Alzheimer's Disease"],"original-title":[],"deposited":{"date-parts":[[2025,2,19]],"date-time":"2025-02-19T13:52:53Z","timestamp":1739973173000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.medra.org\/servlet\/aliasResolver?alias=iospressISSNISBN&issn=2210-5727&volume=01&spage=139"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011]]},"references-count":0,"URL":"https:\/\/doi.org\/10.3233\/978-1-60750-733-8-139","relation":{},"ISSN":["2210-5727"],"issn-type":[{"value":"2210-5727","type":"print"}],"subject":[],"published":{"date-parts":[[2011]]}}}