{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T18:51:59Z","timestamp":1781895119207,"version":"3.54.5"},"reference-count":82,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"25","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2026,6,19]]},"abstract":"<jats:p>\n                    Dysregulation of RNA m\n                    <jats:sup>6<\/jats:sup>\n                    A modification has been implicated in Alzheimer\u2019s disease (AD), but the molecular mechanisms remain largely unclear. Here, we identified the presence of m\n                    <jats:sup>6<\/jats:sup>\n                    A on mitochondria-encoded messenger RNAs (mt-mRNAs) in the brain, with elevated levels correlated with amyloid-\u03b2 (A\u03b2) deposition. Under physiological conditions, cytosolic m\n                    <jats:sup>6<\/jats:sup>\n                    A-modified\n                    <jats:italic toggle=\"yes\">mt-Nd4<\/jats:italic>\n                    is recognized and degraded by the m\n                    <jats:sup>6<\/jats:sup>\n                    A reader protein YTHDF2, thereby preventing aberrant activation of the RIG-I\u2013MAVS innate immune pathway in neurons. Under A\u03b2-associated pathological conditions, YTHDF2 expression is markedly down-regulated in neurons, leading to the accumulation of m\n                    <jats:sup>6<\/jats:sup>\n                    A-modified\n                    <jats:italic toggle=\"yes\">mt-Nd4<\/jats:italic>\n                    in the cytosol. This accumulation triggers RIG-I\u2013MAVS activation and type I interferon (IFN) responses. Neuron-derived IFN-\u03b2 then amplifies neuroinflammation by activating surrounding microglia through a paracrine mechanism. Furthermore, neuronal\n                    <jats:italic toggle=\"yes\">Ythdf2<\/jats:italic>\n                    deficiency exacerbates A\u03b2-associated neuroinflammation and cognitive decline. Together, these findings reveal a previously unrecognized m\n                    <jats:sup>6<\/jats:sup>\n                    A\/YTHDF2-dependent regulatory axis that links mitochondrial RNA metabolism to innate immune activation and neuroinflammation in A\u03b2 pathology.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.adz0887","type":"journal-article","created":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T18:00:33Z","timestamp":1781892033000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Neuronal YTHDF2 suppresses innate immune activation in A\u03b2 pathology by promoting m\n                    <sup>6<\/sup>\n                    A-dependent decay of cytosolic mitochondrial mRNAs"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-5066-1484","authenticated-orcid":true,"given":"Wenqi","family":"Pan","sequence":"first","affiliation":[{"name":"Department of Pathology, Institute of Basic Medical Sciences &amp; School of Basic Medicine, Chinese Academy of Medical Sciences &amp; Peking Union Medical College, Beijing 100005, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1898-8558","authenticated-orcid":true,"given":"Lin","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pathology, Institute of Basic Medical Sciences &amp; School of Basic Medicine, Chinese Academy of Medical Sciences &amp; Peking Union Medical College, Beijing 100005, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-1316-2870","authenticated-orcid":true,"given":"Yao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pathology, Institute of Basic Medical Sciences &amp; School of Basic Medicine, Chinese Academy of Medical Sciences &amp; Peking Union Medical College, Beijing 100005, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pathology, Institute of Basic Medical Sciences &amp; School of Basic Medicine, Chinese Academy of Medical Sciences &amp; Peking Union Medical College, Beijing 100005, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuesi","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Pathology, Institute of Basic Medical Sciences &amp; School of Basic Medicine, Chinese Academy of Medical Sciences &amp; Peking Union Medical College, Beijing 100005, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yifan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pathology, Institute of Basic Medical Sciences &amp; School of Basic Medicine, Chinese Academy of Medical Sciences &amp; Peking Union Medical College, Beijing 100005, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6139-0004","authenticated-orcid":true,"given":"Yujie","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Pathology, Institute of Basic Medical Sciences &amp; 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