{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T03:40:59Z","timestamp":1777434059433,"version":"3.51.4"},"reference-count":102,"publisher":"SAGE Publications","issue":"18","license":[{"start":{"date-parts":[[2015,6,1]],"date-time":"2015-06-01T00:00:00Z","timestamp":1433116800000},"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":["Antioxidants &amp; Redox Signaling"],"published-print":{"date-parts":[[2015,6]]},"abstract":"<jats:p>\n                    <jats:bold>\n                      <jats:italic toggle=\"yes\">Significance:<\/jats:italic>\n                    <\/jats:bold>\n                    A diverse family of lipid-derived levulinaldehydes, isolevuglandins (isoLGs), is produced by rearrangement of endoperoxide intermediates generated through both cyclooxygenase (COX) and free radical-induced cyclooxygenation of polyunsaturated fatty acids and their phospholipid esters. The formation and reactions of isoLGs with other biomolecules has been linked to alcoholic liver disease, Alzheimer's disease, age-related macular degeneration, atherosclerosis, cardiac arythmias, cancer, end-stage renal disease, glaucoma, inflammation of allergies and infection, mitochondrial dysfunction, multiple sclerosis, and thrombosis. This review chronicles progress in understanding the chemistry of isoLGs, detecting their production\n                    <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                    and understanding their biological consequences.\n                    <jats:bold>\n                      <jats:italic toggle=\"yes\">Critical Issues:<\/jats:italic>\n                    <\/jats:bold>\n                    IsoLGs have never been isolated from biological sources, because they form adducts with primary amino groups of other biomolecules within seconds. Chemical synthesis enabled investigation of isoLG chemistry and detection of isoLG adducts present\n                    <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                    .\n                    <jats:bold>\n                      <jats:italic toggle=\"yes\">Recent Advances:<\/jats:italic>\n                    <\/jats:bold>\n                    The first peptide mapping and sequencing of an isoLG-modified protein present in human retina identified the modification of a specific lysyl residue of the sterol C27-hydroxylase Cyp27A1. This residue is preferentially modified by iso[4]LGE\n                    <jats:sub>2<\/jats:sub>\n                    <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                    , causing loss of function. Adduction of less than one equivalent of isoLG can induce COX-associated oligomerization of the amyloid peptide A\u03b2\n                    <jats:sub>1-42<\/jats:sub>\n                    . Adduction of isoLGE\n                    <jats:sub>2<\/jats:sub>\n                    to phosphatidylethanolamines causes gain of function, converting them into proinflammatory isoLGE\n                    <jats:sub>2<\/jats:sub>\n                    -PE agonists that foster monocyte adhesion to endothelial cells.\n                    <jats:bold>\n                      <jats:italic toggle=\"yes\">Future Directions:<\/jats:italic>\n                    <\/jats:bold>\n                    Among the remaining questions on the biochemistry of isoLGs are the dependence of biological activity on isoLG isomer structure, the structures and mechanism of isoLG-derived protein\u2013protein and DNA\u2013protein cross-link formation, and its biological consequences.\n                    <jats:italic toggle=\"yes\">Antioxid. Redox Signal.<\/jats:italic>\n                    22, 1703\u20131718.\n                  <\/jats:p>","DOI":"10.1089\/ars.2014.6154","type":"journal-article","created":{"date-parts":[[2015,1,4]],"date-time":"2015-01-04T10:11:22Z","timestamp":1420366282000},"page":"1703-1718","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":38,"title":["Isolevuglandin Adducts in Disease"],"prefix":"10.1177","volume":"22","author":[{"given":"Robert G.","family":"Salomon","sequence":"first","affiliation":[{"name":"Case Western Reserve University"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenzhao","family":"Bi","sequence":"additional","affiliation":[{"name":"Case Western Reserve University"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2015,6,20]]},"reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1021\/tx0300535"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbalip.2009.02.003"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M103768200"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2004.07.031"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi0257383"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi002629k"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4615-0667-6_16"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M300940200"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2005.03586.x"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2002.01064.x"},{"key":"e_1_3_2_12_2","first-page":"S599","article-title":"Targeting cyclooxygenase-derived levuglandins as potentially novel therapeutic approaches to Alzheimer's disease","volume":"2","author":"Boutaud O","year":"2006","unstructured":"Boutaud O, , Zagol-Ikapitte I, , Amarnath V, , Yermalitsky V, , Andreasson KI, , Montine TJ, , and Oates JA. 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