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A co\u2010immunoprecipitation assay was applied to examine the Thorase\u2010interacting proteins.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>Genetic deletion of Thorase resulted in tau hyperphosphorylation and promoted A\u03b2 accumulation in the mouse brain. Conversely, Thorase overexpression alleviated the pathogenesis of AD. Thorase regulated the phosphorylation of tau by targeting specific kinases and theprotein phosphatase 2B (PP2B). Thorase deficiency also impaired microglial phagocytosis and induced neuroinflammation by the activation of the NOD\u2010like receptor thermal protein domain associated protein 3 (NLRP3)\u00a0inflammasomes in microglia.<\/jats:p><\/jats:sec><jats:sec><jats:title>DISCUSSION<\/jats:title><jats:p>Thorase may be a potential druggable target for developing therapeutic approaches to treat AD and other neurodegenerative diseases.<\/jats:p><\/jats:sec><jats:sec><jats:title>Highlights<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Thorase deletion leads to elevated amyloid beta (A\u03b2) deposition and hyperphosphorylated tau accumulation in the brain.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Thorase regulates the phosphorylation of tau protein via PP2B.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Thorase deficiency impairs microglial phagocytosis and promotesNLRP3\u2010mediated neuroinflammation.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Overexpression of Thorase alleviates A\u03b2 deposition and tau phosphorylation in the AD mouse model.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1002\/alz.14329","type":"journal-article","created":{"date-parts":[[2024,11,13]],"date-time":"2024-11-13T06:49:30Z","timestamp":1731480570000},"page":"8769-8786","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Thorase deficiency causes both A\u03b2 accumulation and tau hyperphosphorylation in mouse brain"],"prefix":"10.1002","volume":"20","author":[{"given":"Han","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Immunology CAMS Key laboratory T cell and Cancer Immunotherapy Institute of Basic Medical Sciences Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, State Key Laboratory of Common Mechanism 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