{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,4]],"date-time":"2025-12-04T10:03:40Z","timestamp":1764842620943,"version":"3.46.0"},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2025,9,20]],"date-time":"2025-09-20T00:00:00Z","timestamp":1758326400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"JSPS KAKENHI","award":["JP16K15333","JP25460388"],"award-info":[{"award-number":["JP16K15333","JP25460388"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,12,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Microglia, the central nervous system's resident macrophages, are critical for immune defense, protecting neurons during infection. Their role in postnatal brain development, particularly after injury, remains unclear. Nucling, a protein up-regulated during cardiac muscle differentiation, regulates NF-\u03baB, influencing apoptosis and cell proliferation. In this study, we examined the role of Nucling in microglial activation using wild-type (WT) and Nucling-knockout (KO) neonatal mice subjected to poly(I:C), a viral mimic. Poly(I:C) treatment increased Iba1-positive microglia in both genotypes; however, KO mice showed a significantly exaggerated response in both cortical and hippocampal regions. Furthermore, while proinflammatory M1 markers (iNOS, CD86, TNF\u03b1, IL-6) were upregulated in both WT and KO mice, the anti-inflammatory M2 marker Arginase 1 (Arg1) was induced in WT but significantly suppressed in KO mice, indicating impaired M2 polarization. These findings suggest that Nucling is essential for maintaining microglial polarization, supporting immunological processes against pathogens and aiding central nervous system development.<\/jats:p>","DOI":"10.1093\/jb\/mvaf055","type":"journal-article","created":{"date-parts":[[2025,9,9]],"date-time":"2025-09-09T11:36:42Z","timestamp":1757417802000},"page":"391-402","source":"Crossref","is-referenced-by-count":0,"title":["Nucling, a stress-inducible protein associated with apoptosomes, is important for microglial polarization\/activation in the brain neuroinflammation"],"prefix":"10.1093","volume":"178","author":[{"given":"Tuan Anh","family":"Pham","sequence":"first","affiliation":[{"name":"Division of Enzyme Pathophysiology, Institute for Enzyme Research, Tokushima University , 3-18-15 Kuramoto-cho, Tokushima 770-8503 ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takashi","family":"Sakai","sequence":"additional","affiliation":[{"name":"Division of Enzyme Pathophysiology, Institute for Enzyme Research, Tokushima University , 3-18-15 Kuramoto-cho, Tokushima 770-8503 ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huy","family":"Van Dang","sequence":"additional","affiliation":[{"name":"Division of Enzyme Pathophysiology, Institute for Enzyme Research, Tokushima University , 3-18-15 Kuramoto-cho, Tokushima 770-8503 ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diem Hong","family":"Tran","sequence":"additional","affiliation":[{"name":"Division of Enzyme Pathophysiology, Institute for Enzyme Research, Tokushima University , 3-18-15 Kuramoto-cho, Tokushima 770-8503 ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuji","family":"Shishido","sequence":"additional","affiliation":[{"name":"Division of Enzyme Pathophysiology, Institute for Enzyme Research, Tokushima University , 3-18-15 Kuramoto-cho, Tokushima 770-8503 ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nam Hoang","family":"Tran","sequence":"additional","affiliation":[{"name":"Division of Enzyme Pathophysiology, Institute for Enzyme Research, Tokushima University , 3-18-15 Kuramoto-cho, Tokushima 770-8503 ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kiyoshi","family":"Fukui","sequence":"additional","affiliation":[{"name":"Division of Enzyme Pathophysiology, Institute for Enzyme Research, Tokushima University , 3-18-15 Kuramoto-cho, Tokushima 770-8503 ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2025,9,20]]},"reference":[{"key":"2025120404515318100_ref1","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1093\/jb\/mvg056","article-title":"Identification of a novel, embryonal carcinoma cell-associated molecule, Nucling, that is up-regulated during cardiac muscle differentiation","volume":"133","author":"Sakai","year":"2003","journal-title":"J. Biochem."},{"key":"2025120404515318100_ref2","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1042\/bj20031300","article-title":"Nucling mediates apoptosis by inhibiting expression of galectin-3 through interference with nuclear factor kappaB signalling","volume":"380","author":"Liu","year":"2004","journal-title":"Biochem. J."},{"key":"2025120404515318100_ref3","doi-asserted-by":"crossref","first-page":"1126","DOI":"10.1111\/j.1471-4159.2006.03833.x","article-title":"Attenuation of MPTP-induced neurotoxicity and locomotor dysfunction in Nucling-deficient mice via suppression of the apoptosome pathway","volume":"97","author":"Teng","year":"2006","journal-title":"J. Neurochem."},{"key":"2025120404515318100_ref4","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1093\/jb\/mvq089","article-title":"NF-kappaB regulates the expression of Nucling, a novel apoptosis regulator, with involvement of proteasome and caspase for its degradation","volume":"148","author":"Tran","year":"2010","journal-title":"J. Biochem."},{"key":"2025120404515318100_ref5","doi-asserted-by":"crossref","first-page":"24626","DOI":"10.1074\/jbc.M115.673848","article-title":"Nucling, a novel apoptosis-associated protein, controls mammary gland involution by regulating NF-\u03baB and STAT3","volume":"290","author":"Dang","year":"2015","journal-title":"J. Biol. Chem."},{"key":"2025120404515318100_ref6","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1093\/jb\/mvs119","article-title":"Nucling, a novel protein associated with NF-\u03baB, regulates endotoxin-induced apoptosis in vivo","volume":"153","author":"Kim","year":"2013","journal-title":"J. Biochem."},{"key":"2025120404515318100_ref7","first-page":"4666","article-title":"Knockdown of UACA inhibits proliferation and invasion and promotes senescence of hepatocellular carcinoma cells","volume":"11","author":"Sun","year":"2018","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"2025120404515318100_ref8","doi-asserted-by":"crossref","first-page":"1600530","DOI":"10.1002\/mnfr.201600530","article-title":"Lycopene inhibits regulator of calcineurin 1-mediated apoptosis by reducing oxidative stress and down-regulating Nucling in neuronal cells","volume":"61","author":"Lim","year":"2017","journal-title":"Mol. Nutr. 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