{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T16:19:54Z","timestamp":1788452394108,"version":"build-2803163510"},"reference-count":80,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T00:00:00Z","timestamp":1775779200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Neurosci."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      The pathogenesis of Parkinson\u2019s disease (PD) has been linked to environmental factors, toxins, genetics, and peripheral inflammation. Importantly, intestinal inflammation like that seen in Crohn\u2019s disease (CD) or food allergies has been implicated in risk for neurodegeneration and late-onset PD. Further, CD and PD share genetic risk factors including gain-of-function leucine-rich repeat kinase 2 (\n                      <jats:italic>LRRK2<\/jats:italic>\n                      ) mutations. Here, we aim to better understand how intestinal inflammation synergizes with\n                      <jats:italic>Lrrk2<\/jats:italic>\n                      levels or kinase activation to promote neurodegeneration in young and old mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We utilized bacterial artificial chromosome (BAC) mice overexpressing wildtype mouse\n                      <jats:italic>Lrrk2<\/jats:italic>\n                      or mutant G2019S mouse\n                      <jats:italic>Lrrk2<\/jats:italic>\n                      and compared them with C57B6J mice at baseline and under conditions of intestinal inflammation using dextran sodium sulfate (DSS) colitis models.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      While our data revealed regulation of the brain inflammatory state by\n                      <jats:italic>Lrrk2<\/jats:italic>\n                      , we did not observe age-dependent selective vulnerability or protection in\n                      <jats:italic>Lrrk2<\/jats:italic>\n                      mouse lines in colitis protocols. Instead, DSS phenotypes were associated with increased nigrostriatal dysregulation in all genotypes independent of age.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>\n                      While\n                      <jats:italic>Lrrk2<\/jats:italic>\n                      mutations appear to influence the genesis of peripheral inflammation, our data suggest that\n                      <jats:italic>Lrrk2<\/jats:italic>\n                      activation due to a gain-of-function mutation does not exacerbate the effects of inflammation on nigrostriatal degeneration in this model.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fncel.2026.1794784","type":"journal-article","created":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T04:26:01Z","timestamp":1775795161000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Intestinal inflammation promotes neuroinflammation and PD-associated nigrostriatal pathology independently of LRRK2 G2019S kinase activity"],"prefix":"10.3389","volume":"20","author":[{"given":"Andrea R.","family":"Merchak","sequence":"first","affiliation":[{"name":"Department of Neuroscience, University of Florida College of Medicine","place":["Gainesville, FL, United States"]},{"name":"Department of Neurology, Stark Neuroscience Research Institute, Indiana University School of Medicine","place":["Indianapolis, IN, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary K.","family":"Herrick","sequence":"additional","affiliation":[{"name":"Department of Physiology, Emory University School of Medicine","place":["Atlanta, GA, United States"]},{"name":"Department of Cell Biology, Emory University School of Medicine","place":["Atlanta, GA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madelyn C.","family":"Houser","sequence":"additional","affiliation":[{"name":"Department of Physiology, Emory University School of Medicine","place":["Atlanta, GA, United States"]},{"name":"Department of Cell Biology, Emory University School of Medicine","place":["Atlanta, GA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cody E.","family":"Keating","sequence":"additional","affiliation":[{"name":"Department of Physiology, Emory University School of Medicine","place":["Atlanta, GA, United States"]},{"name":"Department of Cell Biology, Emory University School of Medicine","place":["Atlanta, GA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianjun","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Physiology, Emory University School of Medicine","place":["Atlanta, GA, United States"]},{"name":"Department of Cell Biology, Emory University School of Medicine","place":["Atlanta, GA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mal\u00fa G\u00e1mez","family":"Tansey","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, University of Florida College of Medicine","place":["Gainesville, FL, United States"]},{"name":"Department of Neurology, Stark Neuroscience Research Institute, Indiana University School of Medicine","place":["Indianapolis, IN, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,10]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"456","DOI":"10.1212\/WNL.57.3.456","article-title":"Frequency of bowel movements and the future risk of Parkinson\u2019s disease","volume":"57","author":"Abbott","year":"2001","journal-title":"Neurology"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1016\/j.parkreldis.2005.07.005","article-title":"Alterations of T-lymphocyte populations in Parkinson disease","volume":"11","author":"Baba","year":"2005","journal-title":"Parkinsonism Relat. 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