{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T18:18:47Z","timestamp":1789755527367,"version":"4.0.1"},"reference-count":30,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2009,1,29]],"date-time":"2009-01-29T00:00:00Z","timestamp":1233187200000},"content-version":"vor","delay-in-days":3622,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[1999,3]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>We previously established that the formation of both \u03b1\u2010 and \u03b2\/\u03b3\u2010secretase\u2010derived products generated by human embryonic kidney 293 cells (HEK293) expressing either wild type or mutant \u03b2APP could be stimulated by agonists of the cyclic AMP\/protein kinase A pathways. This cyclic AMP\u2010dependent effect modulates post\u2010translational events since it is not prevented by actinomycin D or cycloheximide.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>We show here that two protein kinase A inhibitors, H89 and PKI, both trigger dose\u2010dependent inhibition of the basal constitutive production of A\u03b240 and A\u03b242 by HEK293 cells expressing wild type \u03b2APP751.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>H89 also potently inhibits the total A\u03b2 produced by the neocortical neuronal cell line TSM1.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>These two inhibitors also drastically reduce the recovery of A\u03b240 and A\u03b242 produced by HEK293 cells expressing the Swedish (Sw) \u03b2APP and M146V\u2010presenilin 1 (PS1) mutations responsible for cases of the early\u2010onset forms of Familial Alzheimer's disease (FAD).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>By contrast, H89 and PKI do not significantly affect the recovery of the physiological \u03b1\u2010secretase\u2010derived fragment APP\u03b1.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Our study indicates that protein kinase A inhibitors selectively lower the formation of A\u03b240 and A\u03b242 in human cells expressing normal and mutant \u03b2APP and PS1 without affecting the physiological \u03b1\u2010secretase pathway in these cells. Selective inhibitors of protein kinase A may be of therapeutic value in both sporadic and Familial Alzheimer's disease, since they may decrease the production of A\u03b2 that is thought to be responsible for the neurodegenerative process.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (1999) <jats:bold>126<\/jats:bold>, 1186\u20131190; doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0702406\">10.1038\/sj.bjp.0702406<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0702406","type":"journal-article","created":{"date-parts":[[2005,1,28]],"date-time":"2005-01-28T19:42:21Z","timestamp":1106941341000},"page":"1186-1190","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Effect of protein kinase A inhibitors on the production of A\u03b240 and A\u03b242 by human cells expressing normal and Alzheimer's disease\u2010linked mutated \u03b2APP and presenilin 1"],"prefix":"10.1111","volume":"126","author":[{"given":"P","family":"Marambaud","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K","family":"Ancolio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C","family":"Alves da Costa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F","family":"Checler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,1,29]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.1997.69062494.x"},{"key":"e_1_2_6_3_1","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1007\/BF03401708","article-title":"Characterization of new polyclonal antibodies specific for 40 and 42 aminoacid\u2010long amyloid \u03b2 peptides: their use to examine the cell biology of presenilins and the immunohistochemistry of sporadic Alzheimer's disease and cerebral amyloid angiopathy cases","volume":"3","author":"BARELLI H.","year":"1997","journal-title":"Mol. Med."},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)80230-5"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.19.9195"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.8424174"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.89.7.3055"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.1995.65041431.x"},{"key":"e_1_2_6_9_1","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1016\/S0021-9258(17)36041-6","article-title":"A potent synthetic peptide inhibitor of the cAMP\u2010dependent protein kinase","volume":"261","author":"CHENG H\u2010C.","year":"1986","journal-title":"J. Biol. Chem."},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0701151"},{"key":"e_1_2_6_11_1","doi-asserted-by":"crossref","first-page":"5267","DOI":"10.1016\/S0021-9258(19)34116-X","article-title":"Inhibition of forskolin\u2010induced neurite outgrowth and protein phosphorylation by a newly synthesized selective inhibitor of cyclic AMP\u2010dependent protein kinase, N\u2010[2\u2010(p\u2010bromocinnamylamino)ethyl]\u20105\u2010isoquinol:inesulfonamide (H89), of PC12D pheochromocytoma cells","volume":"265","author":"CHIJIWA T.","year":"1990","journal-title":"J. Biol. Chem."},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1006\/mcne.1996.0023"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/360672a0"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm0197-67"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/383710a0"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0394-251"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-291X(92)90442-N"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1295-1291"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-6147(91)90609-V"},{"key":"e_1_2_6_20_1","doi-asserted-by":"crossref","first-page":"22959","DOI":"10.1016\/S0021-9258(19)49409-X","article-title":"Activation of protein kinase C inhibits cellular production of the amyloid \u03b2\u2010protein","volume":"268","author":"HUNG A.Y.","year":"1993","journal-title":"J. Biol. Chem."},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.37.22908"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF03401766"},{"key":"e_1_2_6_23_1","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1007\/BF03401912","article-title":"Proteasome inhibitors prevent the degradation of familial Alzheimer's disease\u2010linked presenilin 1 and trigger increased A\u03b242 secretion by human cells","volume":"4","author":"MARAMBAUD P.","year":"1998","journal-title":"Mol. Medicine"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.1997.68020698.x"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.1997.69062500.x"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.12.6736"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.18-05-01743.1998"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(91)90052-2"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.5.2025"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.12.7977"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm0498-447"}],"container-title":["British Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1038%2Fsj.bjp.0702406","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1038%2Fsj.bjp.0702406","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1038\/sj.bjp.0702406","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,28]],"date-time":"2023-10-28T13:23:45Z","timestamp":1698499425000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1038\/sj.bjp.0702406"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1999,3]]},"references-count":30,"journal-issue":{"issue":"5","published-print":{"date-parts":[[1999,3]]}},"alternative-id":["10.1038\/sj.bjp.0702406"],"URL":"https:\/\/doi.org\/10.1038\/sj.bjp.0702406","archive":["Portico"],"relation":{},"ISSN":["0007-1188","1476-5381"],"issn-type":[{"value":"0007-1188","type":"print"},{"value":"1476-5381","type":"electronic"}],"subject":[],"published":{"date-parts":[[1999,3]]},"assertion":[{"value":"2009-01-29","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}