{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T19:48:37Z","timestamp":1791229717674,"version":"4.1.0"},"reference-count":25,"publisher":"SAGE Publications","issue":"1","license":[{"start":{"date-parts":[[2025,2,17]],"date-time":"2025-02-17T00:00:00Z","timestamp":1739750400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"name":"NIH-NIEHS","award":["R35ES030443-01"],"award-info":[{"award-number":["R35ES030443-01"]}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Alzheimer\u2019s Disease"],"published-print":{"date-parts":[[2025,3]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Alzheimer's disease (AD) and its monoclonal antibody therapies are associated with brain vasculitis and amyloid-related imaging abnormalities. The naturally-formed epoxides (EpFAs) of polyunsaturated fatty acids (PUFAs), such as 11,12-epoxyeicosatetraenoic acid (EEQ), are anti-inflammatory and pro-resolution mediators, which are increased by dietary supplementation with \u03c9-3 PUFAs. EpFAs are, however, enzymatically hydrolyzed by soluble epoxide hydrolase (sEH) in AD patients' macrophages in vivo and in vitro\n                      <jats:italic toggle=\"yes\">.<\/jats:italic>\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To repair amyloid-\u03b2 1-42 (A\u03b2) degradation by AD macrophages using the inhibitors of a) soluble epoxide hydrolase (sEHIs), termed TPPU and EC5026, together with EpFAs, or b) STING pathway termed H-151.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Immunobiology, immunochemistry, RNA sequencing, and confocal microscopy were used.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In AD brain (examined postmortem), monocyte\/macrophages upload A\u03b2 in plaques and transfer it without degradation into brain microvessels, suffer apoptotis, and release A\u03b2, inducing vasculitis. The EpFAs of epoxyeicosatetraenoic acid (EEQ), along with the inhibitors TPPU and H-151, decrease inflammatory cytokines and regulate macrophage unfolded protein response to endoplasmic reticulum stress. Treatment of AD macrophages by TPPU with EEQ or by STING inhibitor H-151 increased uploading of A\u03b2 after 2\u2005hours and increased degradation of A\u03b2 after 24\u2005hours.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The sEHI inhibitor EC5026 and the STING inhibitor H-151 increased macrophage uptake and degradation of A\u03b2. EC5026 administration was safe in normal volunteers. EC5026 together with \u03c9-3 PUFA supplementation are indicated for in a clinical trial in patients with mild cognitive impairment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/13872877241305965","type":"journal-article","created":{"date-parts":[[2025,2,18]],"date-time":"2025-02-18T02:48:56Z","timestamp":1739846936000},"page":"150-157","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":9,"title":["Inhibitors of soluble epoxide hydrolase and cGAS\/STING repair defects in amyloid-\u03b2 clearance underlying vascular complications of Alzheimer's disease"],"prefix":"10.1177","volume":"104","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-5212-0123","authenticated-orcid":false,"given":"Milan","family":"Fiala","sequence":"first","affiliation":[{"name":"Department of Integrative Biology and Physiology, UCLA School of Medicine, Los Angeles, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce D","family":"Hammock","sequence":"additional","affiliation":[{"name":"Department of Entomology and Nematology, UC Davis Comprehensive Cancer Center University of California-Davis, Davis, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9891-928X","authenticated-orcid":false,"given":"Sung Hee","family":"Hwang","sequence":"additional","affiliation":[{"name":"Department of Entomology and Nematology, UC Davis Comprehensive Cancer Center University of California-Davis, Davis, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2763-7733","authenticated-orcid":false,"given":"Julian","family":"Whitelegge","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, UCLA School of Medicine, Los Angeles, CA, 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