{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,21]],"date-time":"2026-06-21T13:56:16Z","timestamp":1782050176339,"version":"3.54.5"},"reference-count":49,"publisher":"SAGE Publications","issue":"4","license":[{"start":{"date-parts":[[2016,9,11]],"date-time":"2016-09-11T00:00:00Z","timestamp":1473552000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Alzheimer\u2019s Disease"],"published-print":{"date-parts":[[2016,10,18]]},"abstract":"<jats:p>\n                    In Alzheimer\u2019s disease (AD), the amyloid cascade hypothesis proposes that amyloid-beta (A\u03b2) neurotoxicity leads to neuroinflammation, synaptic loss, and neuronal degeneration. In AD patients, anti-amyloid immunotherapies did not succeed because they were possibly administered late in AD progression. Modulating new targets associated with A\u03b2 toxicity, such as PKR (double-stranded RNA dependent kinase), and JNK (c-Jun N-terminal kinase) is a major goal for neuroprotection. These two pro-apoptotic kinases are activated in AD brains and involved in A\u03b2 production, tau phosphorylation, neuroinflammation, and neuronal death. In HEK cells transfected with siRNA directed against PKR, and in PKR knockout (PKR\n                    <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    ) mice neurons, we showed that PKR triggers JNK activation. A\u03b2-induced neuronal apoptosis, measured by cleaved PARP (Poly ADP-ribose polymerase) and cleaved caspase 3 levels, was reduced in PKR\n                    <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    neurons. Two selective JNK inhibitory peptides also produced a striking reduction of A\u03b2 toxicity. Finally, the dual inhibition of PKR and JNK nearly abolished A\u03b2 toxicity in primary cultured neurons. These results reveal that dual kinase inhibition can afford neuroprotection and this approach is worth being tested in\n                    <jats:italic>in vivo<\/jats:italic>\n                    AD and oxidative stress models.\n                  <\/jats:p>","DOI":"10.3233\/jad-160509","type":"journal-article","created":{"date-parts":[[2016,9,13]],"date-time":"2016-09-13T14:42:34Z","timestamp":1473777754000},"page":"1659-1670","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":17,"title":["Dual Kinase Inhibition Affords Extended in\u00a0vitro Neuroprotection in Amyloid-\u03b2 Toxicity"],"prefix":"10.1177","volume":"54","author":[{"given":"Sarah","family":"Gourmaud","sequence":"first","affiliation":[{"name":"Inserm UMR-S 942, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fran\u00e7ois","family":"Mouton-Liger","sequence":"additional","affiliation":[{"name":"Brain and Spine Institute, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire","family":"Abadie","sequence":"additional","affiliation":[{"name":"Solid Drug Development, Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eliane F.","family":"Meurs","sequence":"additional","affiliation":[{"name":"Institut Pasteur, Hepacivirus and Innate Immunity Unit, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire","family":"Paquet","sequence":"additional","affiliation":[{"name":"Inserm UMR-S 942, Paris, France"},{"name":"Research Memory Centre, Paris Nord Ile de France Saint Louis Lariboisi\u00e8re Fernand Widal Hospital, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacques","family":"Hugon","sequence":"additional","affiliation":[{"name":"Inserm UMR-S 942, Paris, France"},{"name":"Research Memory Centre, Paris Nord Ile de France Saint Louis Lariboisi\u00e8re Fernand Widal Hospital, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2016,9,11]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-009-0532-1"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1566067"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0073631"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2013.154"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-2008-15215"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/path.4491"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2002.01237.x"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1042\/bst0250509"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1097\/00001756-200212200-00011"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2008.10.047"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0053587"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2011.11.031"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep08489"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2014.552"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)00116-1"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2006.12.009"},{"key":"e_1_3_3_18_2","first-page":"140062","article-title":"Increased levels of cerebrospinal fluid JNK3 associated with amyloid pathology: Links to cognitive decline","volume":"39","author":"Gourmaud S","year":"2014","unstructured":"GourmaudS, PaquetC, DumurgierJ, PaceC, BourasC, GrayF, LaplancheJL, MeursEF, Mouton-LigerF, HugonJ (2014) Increased levels of cerebrospinal fluid JNK3 associated with amyloid pathology: Links to cognitive decline. 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