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The activation of calcium-dependent cytosolic phospholipase A\n                      <jats:sub>2<\/jats:sub>\n                      (cPLA2) is involved in inflammatory signaling and is elevated within the plaques of AD brains. The relation between\n                      <jats:italic>APOE4<\/jats:italic>\n                      genotype and cPLA2 activity is not known.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Mouse primary astrocytes, mouse and human brain samples differing by\n                      <jats:italic>APOE<\/jats:italic>\n                      genotypes were collected for measuring cPLA2 expression, phosphorylation, and activity in relation to measures of inflammation and oxidative stress.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Greater cPLA2 phosphorylation, cPLA2 activity and leukotriene B4 (LTB4) levels were identified in ApoE4 compared to ApoE3 in primary astrocytes, brains of ApoE-targeted replacement (ApoE-TR) mice, and in human brain homogenates from the inferior frontal cortex of persons with AD dementia carrying\n                      <jats:italic>APOE3\/4<\/jats:italic>\n                      compared to\n                      <jats:italic>APOE3\/3<\/jats:italic>\n                      . Higher phosphorylated p38 MAPK but not ERK1\/2 was found in ApoE4 primary astrocytes and mouse brains than that in ApoE3. Greater cPLA2 translocation to cytosol was observed in human postmortem frontal cortical synaptosomes with recombinant ApoE4 than ApoE3 ex vivo. In ApoE4 astrocytes, the greater levels of LTB4, reactive oxygen species (ROS), and inducible nitric oxide synthase (iNOS) were reduced after cPLA2 inhibition.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Our findings implicate greater activation of cPLA2 signaling system with\n                      <jats:italic>APOE4<\/jats:italic>\n                      , which could represent a potential drug target for mitigating the increased neuroinflammation with\n                      <jats:italic>APOE4<\/jats:italic>\n                      and AD.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13024-022-00549-5","type":"journal-article","created":{"date-parts":[[2022,6,15]],"date-time":"2022-06-15T08:03:18Z","timestamp":1655280198000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":66,"title":["Calcium-dependent cytosolic phospholipase A2 activation is implicated in neuroinflammation and oxidative stress associated with ApoE4"],"prefix":"10.1186","volume":"17","author":[{"given":"Shaowei","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boyang","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria","family":"Solomon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfred","family":"Fonteh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stanley I.","family":"Rapoport","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Bennett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zoe","family":"Arvanitakis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helena C.","family":"Chui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick M.","family":"Sullivan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2483-649X","authenticated-orcid":false,"given":"Hussein N.","family":"Yassine","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,6,15]]},"reference":[{"key":"549_CR1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/S1388-1981(00)00105-0","volume":"1488","author":"DA Six","year":"2000","unstructured":"Six DA, Dennis EA. 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The frozen inferior frontal lobe (Brodmann area 10) was obtained from the Rush Alzheimer\u2019s Disease Center (RADC) at the Rush University Medical Center. Rush Memory and Aging Project was approved by an Institutional Review Board (IRB) of Rush University Medical Center.The USC Animal Care Committee approved the mouse studies.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"42"}}