{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T11:27:04Z","timestamp":1769513224382,"version":"3.49.0"},"reference-count":52,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2012,5,23]],"date-time":"2012-05-23T00:00:00Z","timestamp":1337731200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2012,9]]},"abstract":"<jats:sec><jats:label\/><jats:p><jats:italic>J. Neurochem<\/jats:italic>. (2012) <jats:bold>122<\/jats:bold>, 952\u2013961.<\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>While free radicals and inflammation constitute major routes of neuronal injury occurring in amyotrophic lateral sclerosis (ALS), neither antioxidants nor non\u2010steroidal anti\u2010inflammatory drugs have shown significant efficacy in human clinical trials. We examined the possibility that concurrent blockade of free radicals and prostaglandin E<jats:sub>2<\/jats:sub> (PGE<jats:sub>2<\/jats:sub>)\u2010mediated inflammation might constitute a safe and effective therapeutic approach to ALS. We have developed 2\u2010hydroxy\u20105\u2010[2\u2010(4\u2010trifluoromethylphenyl)\u2010ethylaminobenzoic acid] (AAD\u20102004) as a derivative of aspirin. AAD\u20102004 completely removed free radicals at 50\u2003nM as a potent spin\u2010trapping molecule and inhibited microsomal PGE<jats:sub>2<\/jats:sub> synthase\u20101 (mPGES\u20101) activity in response to both lipopolysaccharide\u2010treated BV2 cell with IC<jats:sub>50<\/jats:sub> of 230\u2003nM and recombinant human mPGES\u20101 protein with IC<jats:sub>50<\/jats:sub> of 249\u2003nM <jats:italic>in vitro<\/jats:italic>. In superoxide dismutase 1<jats:sup>G93A<\/jats:sup> transgenic mouse model of ALS, AAD\u20102004 blocked free radical production, PGE<jats:sub>2<\/jats:sub> formation, and microglial activation in the spinal cords. As a consequence, AAD\u20102004 reduced autophagosome formation, axonopathy, and motor neuron degeneration, improving motor function and increasing life span. In these assays, AAD\u20102004 was superior to riluzole or ibuprofen. Gastric bleeding was not induced by AAD\u20102004 even at a dose 400\u2010fold higher than that required to obtain maximal therapeutic efficacy in superoxide dismutase 1<jats:sup>G93A<\/jats:sup>. Targeting both mPGES\u20101\u2010mediated PGE<jats:sub>2<\/jats:sub> and free radicals may be a promising approach to reduce neurodegeneration in ALS and possibly other neurodegenerative diseases.<\/jats:p><\/jats:sec>","DOI":"10.1111\/j.1471-4159.2012.07771.x","type":"journal-article","created":{"date-parts":[[2012,4,26]],"date-time":"2012-04-26T16:38:07Z","timestamp":1335458287000},"page":"952-961","source":"Crossref","is-referenced-by-count":34,"title":["Concurrent blockade of free radical and microsomal prostaglandin E synthase\u20101\u2010mediated PGE<sub>2<\/sub> production improves safety and efficacy in a mouse model of amyotrophic lateral sclerosis"],"prefix":"10.1111","volume":"122","author":[{"given":"Jin Hee","family":"Shin","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Young Ae","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jae Keun","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yong Beom","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Woong","family":"Cho","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Doo Soon","family":"Im","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jin Hwan","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bok Sun","family":"Yun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joe E.","family":"Springer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Byoung Joo","family":"Gwag","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2012,5,23]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/1531-8249(20010201)49:2<176::AID-ANA37>3.0.CO;2-X"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/00001756-200008030-00029"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-007-9564-x"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410420416"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2006.12.015"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.1993.tb07478.x"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2007.10.015"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.4161\/auto.5432"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/232017a0"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.20552"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.20903"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pharmtox.47.120505.105237"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1080\/146608201300079364"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1006\/abbi.1994.1485"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.10374"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/35068632"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00109-001-0289-z"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn1137"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI18162"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.128.5.877"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.1997.69052064.x"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pathophys.2006.08.003"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2003.10.004"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1080\/17482960802195632"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00702-004-0220-1"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.8209258"},{"key":"e_1_2_8_28_1","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1212\/WNL.50.1.62","article-title":"Riluzole preserves motor function in a transgenic model of familial amyotrophic lateral sclerosis","volume":"50","author":"Gurney M. 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