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Microglial\u2010mediated brain inflammation is thought to play key roles in AD progression. Clinical evidence and animal models have indicated that the ribosome\u2010associated quality control (RQC) component Listerin is involved in the development of AD. How Listerin regulates the development and progression of AD is unknown. Here, it is demonstrated that Listerin can decrease brain inflammation and alleviate AD\u2010related cognitive impairments. Microglial\u2010specific knockout of Listerin exhibits deteriorative cognitive symptoms based on the extracellular Amyloid\u2010\u03b2 (A\u03b2) or Lipopolysaccharide (LPS) injection. Mechanistically, Listerin directly binds to Toll\u2010like receptor 4 (TLR4) mRNA and facilitates the IRE1\u03b1\u2010mediated cleavage and degradation of\n                    <jats:italic>TLR4<\/jats:italic>\n                    mRNA, leading to the alleviation of TLR4\u2010induced brain inflammation. Adenovirus\u2010mediated overexpression of Listerin decelerates the disease progression in the mouse model of A\u03b2\u2010mediated neurodegeneration. Thus, Listerin is an important suppressor of microglia\u2010induced brain inflammation and may be a potential therapeutic target for AD treatment.\n                  <\/jats:p>","DOI":"10.1002\/advs.202414956","type":"journal-article","created":{"date-parts":[[2025,5,31]],"date-time":"2025-05-31T08:54:48Z","timestamp":1748681688000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Listerin Alleviates Alzheimer's Disease through IRE1\u2010mediated Decay of\n                    <i>TLR4<\/i>\n                    mRNA"],"prefix":"10.1002","volume":"12","author":[{"given":"Fei","family":"Qin","sequence":"first","affiliation":[{"name":"Key Laboratory of Infection Immunity and prevention of Shandong Province &amp; Key Laboratory for Experimental Teratology of Ministry of Education Shandong University  Jinan Shandong 250012 P. R. 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