{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T15:50:24Z","timestamp":1791561024532,"version":"4.3.4"},"reference-count":80,"publisher":"Wiley","issue":"21","license":[{"start":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T00:00:00Z","timestamp":1786579200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T00:00:00Z","timestamp":1786579200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2026,11]]},"abstract":"<jats:sec>\n                    <jats:title>Background and Purpose<\/jats:title>\n                    <jats:p>Patients with Parkinson's disease (PD) show intestinal epithelial barrier (IEB) alterations, enteric gliosis and inflammation that could contribute to gastrointestinal symptoms. Moreover, changes in leucine rich\u2010repeat kinase 2 (LRRK2) expression\/activity have been associated with PD development and related intestinal inflammation. However, the molecular determinants linking LRRK2, enteric gliosis and IEB impairment remain unclear. Therefore, we investigated the role of LRRK2 in IEB changes associated with PD, focusing on its role in the interplay between enteric glial cells (EGCs) and intestinal epithelial cells (IECs).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>\n                      Human A53T \u03b1\u2010synuclein transgenic (Tg) mice (9\u00a0months old) were provided a model of early PD. Central neuroinflammation was studied by IBA\u20101 staining. Intestinal motility, colonic \u03b1\u2010synuclein and LRRK2 expression were assessed. Enteric gliosis was evaluated by detection of GFAP\n                      <jats:sup>+<\/jats:sup>\n                      cells co\u2010expressing LRRK2; IEB was tested by mucins detection and quantification of Muc\u20102, tight junction proteins and secretory autophagy. In vitro co\u2010cultures between EGCs and IECs were performed to investigate glial LRRK2\u2010mediated gut barrier alterations.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>\n                      A53T mice, without central neuroinflammation, showed intestinal disturbances, colonic \u03b1\u2010synuclein accumulation and an increase in colonic GFAP\n                      <jats:sup>+<\/jats:sup>\n                      \/LRRK2\n                      <jats:sup>+<\/jats:sup>\n                      glial cells before brain pathology. Moreover, PD animals displayed IEB alterations and increased colonic autophagosomes, suggesting a shift towards secretory autophagy. In co\u2010culture experiments, \u03b1\u2010synuclein and lipopolysaccharide promoted enteric gliosis and LRRK2 up\u2010regulation in glial cells, contributing to IEB impairment via secretory autophagy.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions and Implications<\/jats:title>\n                    <jats:p>These changes could influence bowel symptoms and central pathology associated with PD, via the gut\u2010brain axis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.70623","type":"journal-article","created":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T14:37:36Z","timestamp":1786631856000},"page":"6534-6553","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Up\u2010regulation of the kinase LRRK2, in enteric glia contributes to mucosal barrier impairment in Parkinson's disease via secretory autophagy"],"prefix":"10.1111","volume":"183","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3303-0674","authenticated-orcid":false,"given":"Vanessa","family":"D'Antongiovanni","sequence":"first","affiliation":[{"name":"Unit of Human Histology and Embryology, Department of Clinical and Experimental Medicine University of Pisa  Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-8288-2888","authenticated-orcid":false,"given":"Clarissa","family":"Pierucci","sequence":"additional","affiliation":[{"name":"Unit of Human Histology and Embryology, Department of Clinical and Experimental Medicine University of Pisa  Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3983-1333","authenticated-orcid":false,"given":"Cristina","family":"Segnani","sequence":"additional","affiliation":[{"name":"Unit of Human Histology and Embryology, Department of Clinical and Experimental Medicine 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