{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,2]],"date-time":"2025-08-02T16:25:06Z","timestamp":1754151906645,"version":"3.41.2"},"reference-count":26,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2025,5,22]],"date-time":"2025-05-22T00:00:00Z","timestamp":1747872000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Increased phospholipase C epsilon 1 (PLCE1) gene expression has been observed in patients with Alzheimer disease (AD), but its roles in AD remain unclear. This study aimed to explore the effects of PLCE1 expression in AD models. Rats were divided into 4 groups: sham+AAV-shNC (negative control), sham+AAV-shPLCE1, A\u03b2+AAV-shNC, and A\u03b2 + AAV-shPLCE1. To investigate the effects of PLCE1 expression following \u03b2-amyloid administration, its expression was measured at both the mRNA and protein levels. Cognitive function was assessed using the Morris water maze. Immunofluorescence and Nissl staining of cerebral cortical tissues demonstrated that PLCE1 downregulation alleviated \u03b2-amyloid-induced brain injury. TUNEL, Western blot, and Enzyme-linked Immunosorbent Assay (ELISA) assays also showed that PLCE1 downregulation inhibited pyroptosis and inflammatory markers in the rats and in SH-SY5Y neuroblastoma cells. Using MTT, TUNEL, Western blot, and ELISA assays, we found that upregulation of the GTPase RAC1, which belongs to the RAS superfamily of small GTP-binding proteins, reversed the neuroprotective effect of PLCE1 downregulation. Together, this study suggests that PLCE1 may worsen AD by activating the STAT3 pathway through RAC1 upregulation. Overall, PLCE1 may exacerbate \u03b2-amyloid-induced cognitive impairments and pyroptosis via the RAC1-STAT3 pathway in AD patients.<\/jats:p>","DOI":"10.1093\/jnen\/nlaf048","type":"journal-article","created":{"date-parts":[[2025,5,22]],"date-time":"2025-05-22T12:45:51Z","timestamp":1747917951000},"page":"734-745","source":"Crossref","is-referenced-by-count":0,"title":["Phospholipase C epsilon 1 aggravates \u03b2-amyloid-associated cognitive impairments and pyroptosis through activating the RAC1-STAT3 pathway in Alzheimer disease models"],"prefix":"10.1093","volume":"84","author":[{"given":"Lijuan","family":"Pei","sequence":"first","affiliation":[{"name":"Department of Neurology, The Third People\u2019s Hospital of Gansu Province , Lanzhou, Gansu,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenjuan","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Neurology, The Third People\u2019s Hospital of Gansu Province , Lanzhou, 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