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Bull."],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Interleukin-33 (IL-33) regulates immune responses in central nervous system diseases. This study investigates the effect of IL-33 on astrocyte phenotypic transformation in Parkinson\u2019s disease (PD). The associations of IL-33, soluble growth-stimulating expression gene 2 (sST2), with PD severity and clinical symptoms were examined. IL-33 supplementation and knockdown were applied\n                    <jats:italic>in vivo<\/jats:italic>\n                    and\n                    <jats:italic>in vitro<\/jats:italic>\n                    to assess IL-33\u2019s impact on neuron loss, astrocyte polarization, and inflammation. Transcriptome sequencing was conducted to identify hub genes and pathways regulated by IL-33 in astrocytes, with validated in primary astrocytes. Plasma sST2 levels were elevated in PD patients and correlated with PD severity, while IL-33 decreased with disease progression. In PD models, IL-33 supplementation improved PD-like symptoms and A2 astrocyte polarization. Conversely, IL-33 knockdown worsened PD-like symptoms and neurotoxic polarization. RNA-seq identified the PENK-ERK\/MAPK pathway as the key regulator of IL-33-mediated astrocyte transformation. In conclusion, IL-33 plays a crucial role in regulating astrocytes in PD.\n                  <\/jats:p>","DOI":"10.1007\/s12264-025-01566-2","type":"journal-article","created":{"date-parts":[[2026,1,3]],"date-time":"2026-01-03T08:51:29Z","timestamp":1767430289000},"page":"1551-1568","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["IL-33 Regulates the Phenotypic Transformation of Reactive Astrocytes via PENK-ERK\/MAPK Pathway in Parkinson\u2019s Disease"],"prefix":"10.1007","volume":"42","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2303-4927","authenticated-orcid":false,"given":"Yi","family":"Qu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhijuan","family":"Mao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danlei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke","family":"An","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoheng","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qixiong","family":"Qin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingyi","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongjie","family":"Xiong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhe","family":"Min","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8204-9945","authenticated-orcid":false,"given":"Zheng","family":"Xue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,1,3]]},"reference":[{"key":"1566_CR1","doi-asserted-by":"publisher","first-page":"368","DOI":"10.1136\/jnnp.2007.131045","volume":"79","author":"J Jankovic","year":"2008","unstructured":"Jankovic J. 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