{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T16:12:50Z","timestamp":1777392770680,"version":"3.51.4"},"reference-count":51,"publisher":"SAGE Publications","issue":"1","license":[{"start":{"date-parts":[[2024,1,9]],"date-time":"2024-01-09T00:00:00Z","timestamp":1704758400000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Alzheimer's Disease Reports"],"published-print":{"date-parts":[[2024,1,9]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Glycogen synthase-3 kinase (GSK3) is one of the major contributors of tau hyperphosphorylation linked to neurofibrillary tangles in Alzheimer\u2019s disease (AD).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>To determine a mechanism of GSK-3\u03b2 activation by two periodontal bacteria consistently confirmed in AD autopsied brains.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>Porphyromonas gingivalis FDC381 and Actinomyces naeslundii ATCC10301 conditioned media were collected. IMR-32 cells were challenged for 48\u200ah with the conditioned media alongside P. gingivalis (ATCC33277) ultrapurified lipopolysaccharide (LPS) designated Pg.LPS under established cell culture conditions either alone or combined. Gene expression and protein analyses for GSK-3\u03b2 were carried out.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>qPCR demonstrated that GSK-3\u03b2 gene was overexpressed in IMR-32 cells treated with Pg.LPS with a 2.09-fold change ( p\u200a=\u200a0.0005), while A. naeslundii treated cells demonstrated 1.41-fold change ( p\u200a=\u200a0.004). Western blotting of the cells challenged with Pg.LPS ( p\u200a=\u200a0.01) and A. naeslundii conditioned medium ( p\u200a=\u200a0.001) demonstrated the 37 kDa band for each treatment with variable intensity across the medium control. Immunohistochemistry with the GSK-3\u03b2 of the IMR-32 cells challenged with Pg.LPS and A. naeslundii alone demonstrated cytoplasmic and nuclear localization.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>Exposure to various bacterial factors upregulated the gene expression of GSK-3\u03b2. Western blotting for GSK-3\u03b2 confirmed the presence of the cleaved fragment by Pg.LPS (37\u200akDa band p\u200a=\u200a0.01) and A. naeslundii conditioned medium (37\u200akDa band p\u200a=\u200a0.001). Immunostaining demonstrated both cytoplasmic and nuclear localization of GSK-3\u03b2. Therefore, Pg.LPS and an unknown factor from the A. naeslundii conditioned medium mediated GSK-3\u03b2 activation via its transcriptionally active, cleaved, fragment. These virulence factors in the body appear to be detrimental to brain health.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3233\/adr-240066","type":"journal-article","created":{"date-parts":[[2024,7,19]],"date-time":"2024-07-19T11:43:18Z","timestamp":1721389398000},"page":"1055-1067","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":5,"title":["<i>Porphyromonas gingivalis<\/i>\n                    LPS and\n                    <i>Actinomyces naeslundii<\/i>\n                    Conditioned Medium Enhance the Release of a Low Molecular Weight, Transcriptionally Active, Fragment of Glycogen Synthase-3 Kinase in IMR-32 Cell Line"],"prefix":"10.1177","volume":"8","author":[{"given":"Sim K.","family":"Singhrao","sequence":"first","affiliation":[{"name":"School of Medicine and Dentistry, University of Central Lancashire, Preston, 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