{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T04:20:35Z","timestamp":1761711635040,"version":"build-2065373602"},"reference-count":71,"publisher":"Wiley","issue":"15","license":[{"start":{"date-parts":[[2003,10,16]],"date-time":"2003-10-16T00:00:00Z","timestamp":1066262400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000957","name":"Alzheimer's Association","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000957","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2003,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Increased Ser phosphorylation of\n                    <jats:italic>tau<\/jats:italic>\n                    microtubule\u2010associated protein in the brain is an early feature of Alzheimer's disease (AD) that precedes progression of the disease to frank neuronal disruption. We demonstrate that bradykinin (BK) B\n                    <jats:sub>2<\/jats:sub>\n                    receptor activation leads to selective Ser phosphorylation of\n                    <jats:italic>tau<\/jats:italic>\n                    in skin fibroblasts from persons who have or will develop AD due to Presenilin 1 mutations or Trisomy 21, but not in skin fibroblasts from normal individuals at any age. The increased signal transduction in AD fibroblasts that culminates in\n                    <jats:italic>tau<\/jats:italic>\n                    Ser phosphorylation reflects modification of the G protein\u2010coupled BK B2 receptors themselves. Both the BK B2 receptor modification and BK\u2010mediated\n                    <jats:italic>tau<\/jats:italic>\n                    Ser phosphorylation are dependent on activation of protein kinase C and can be detected in fibroblasts from persons with Trisomy 21 two decades before the characteristic onset of AD. This dysregulated signaling cascade in AD may thus be expressed throughout life as an aberrant pathway in peripheral tissues more accessible than brain for molecular analysis. The sites of greatest BK B\n                    <jats:sub>2<\/jats:sub>\n                    receptor expression in brain overlap with those areas displaying the earliest pathology in the course of AD, suggesting that BK receptor pathway dysfunction may be a molecular signature yielding information about the pathogenesis of AD.\n                  <\/jats:p>","DOI":"10.1096\/fj.02-1147fje","type":"journal-article","created":{"date-parts":[[2003,10,20]],"date-time":"2003-10-20T20:21:40Z","timestamp":1066681300000},"page":"2319-2321","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Alzheimer's disease skin fibroblasts selectively express a bradykinin signaling pathway mediating\n                    <i>tau<\/i>\n                    protein Ser phosphorylation"],"prefix":"10.1096","volume":"17","author":[{"given":"Yuh-Jiin I.","family":"Jong","sequence":"first","affiliation":[{"name":"Department of Anatomy and Neurobiology Washington University School of Medicine St. Louis MO"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephanie R.","family":"Ford","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Neurobiology Washington University School of Medicine St. Louis MO"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kuljeet","family":"Seehra","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Neurobiology Washington University School of Medicine St. Louis MO"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Victor Brian","family":"Malave","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Neurobiology Washington University School of Medicine St. Louis MO"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nancy Lewis","family":"Baenziger","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Neurobiology Washington University School of Medicine St. Louis MO"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2003,10,16]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1096\/fasebj.5.3.2001787"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)80230-5"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/375754a0"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.48.32322"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.89.7.3055"},{"key":"e_1_2_6_7_1","doi-asserted-by":"crossref","first-page":"21097","DOI":"10.1016\/S0021-9258(19)36898-X","article-title":"Regulation by phorbol esters of amyloid precursor protein release from Swiss 3T3 fibroblasts overexpressing protein kinase C alpha","volume":"268","author":"Slack B. 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