{"id":600,"date":"2026-06-29T00:40:56","date_gmt":"2026-06-28T15:40:56","guid":{"rendered":"https:\/\/neuroclub.jikei-neuroscience.com\/?p=600"},"modified":"2026-06-29T00:40:56","modified_gmt":"2026-06-28T15:40:56","slug":"neuroclub-2026-7-1-%e6%8b%85%e5%bd%93-%e4%b9%85%e4%bf%9d%e5%81%a5%e4%b8%80%e9%83%8e","status":"publish","type":"post","link":"https:\/\/neuroclub.jikei-neuroscience.com\/?p=600","title":{"rendered":"Neuroclub 2026-7-1 \u62c5\u5f53 \u4e45\u4fdd\u5065\u4e00\u90ce"},"content":{"rendered":"

7\/1\u62c5\u5f53\u306e\u4e45\u4fdd\u5065\u4e00\u90ce\uff08\u89e3\u5256\u5b66\u8b1b\u5ea7\uff09\u3067\u3059\u3002
\n\u5f53\u65e5\u306f\u3001\u4e0b\u8a18\u306e\u8ad6\u6587\u3092\u7d39\u4ecb\u3055\u305b\u3066\u9802\u304f\u4e88\u5b9a\u3067\u3059\u3002<\/p>\n

DNA damage burden causes selective CUX2 neuron loss in neuroinflammation<\/strong><\/p>\n

Nature.<\/strong> 2026 May;653(8115):809-818. doi: 10.1038\/s41586-026-10310-3. Epub 2026 Apr 1.<\/p>\n

PMID: 41922773<\/p>\n

PMCID: PMC13190333<\/p>\n

DOI: 10.1038\/s41586-026-10310-3<\/p>\n

Abstract\uff1b
\nNeurodegeneration shows regional and cell-type-specific patterns in ageing and disease1, but the underlying mechanisms for cell-type-specific neuronal losses remain poorly understood. Previous studies have shown that upper cortical layer thinning occurs in progressive human multiple sclerosis (MS) and that cortical layer 2 and layer 3 (L2\/3) excitatory neurons (L2\/3ENs) that express CUT-like homeobox 2 (CUX2) are selectively vulnerable to degeneration2. Here we report that L2\/3ENs within MS cortical lesions have an elevated DNA damage burden. DNA damage and selective loss of L2\/3ENs were recapitulated in diverse mouse models of demyelination and pan-cortical inflammation, confirming their intrinsic vulnerability. Functions of Cux2 and activating transcription factor 4 (Atf4) were essential for resilience of L2\/3ENs during postnatal neuroinflammation, acting in neurons to enhance DNA double-strand break repair. Interferon-\u03b3, a cytokine implicated in MS pathogenesis3,4, was sufficient to elevate levels of reactive oxygen species, leading to DNA damage-mediated neuronal death in vitro, and caused selective depletion of L2\/3 neurons in mice. These findings indicate that DNA damage burden and inadequate repair in CUX2+ L2\/3ENs contributes to selective vulnerability in neuroinflammatory injury.<\/p>\n

\u4ee5\u4e0b\u306elink\u3088\u308a\u3001Open access\u306e\u8ad6\u6587\u3067\u3059\u3002<\/p>\n\n\n\n
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nature.com<\/a><\/td>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

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\u4e45\u4fdd\u5065\u4e00\u90ce<\/p>\n

\uff0a\uff0a\uff0a\uff0a\uff0a\uff0a\uff0a\uff0a\uff0a\uff0a\uff0a\uff0a\uff0a\uff0a\uff0a\uff0a\uff0a\uff0a\uff0a\uff0a\uff0a\uff0a\uff0a\uff0a<\/p>\n

\u6771\u4eac\u6148\u6075\u4f1a\u533b\u79d1\u5927\u5b66\u89e3\u5256\u5b66\u8b1b\u5ea7<\/p>\n

\u3012105-8461\u3000\u6771\u4eac\u90fd\u6e2f\u533a\u897f\u65b0\u6a4b\uff13\u4e01\u76ee\uff12\uff15\u756a\uff18\u53f7\u3000<\/p>\n

\u5185\u7dda\uff1a2206 \u3000Tel\uff1a03-3433-1111\uff08\u5927\u4ee3\u8868\uff09<\/p>\n

ken16<\/p>\n

kennykubo<\/p>\n

\uff0a\uff0a\uff0a\uff0a\uff0a\uff0a\uff0a\uff0a\uff0a\uff0a\uff0a\uff0a\uff0a\uff0a\uff0a\uff0a\uff0a\uff0a\uff0a\uff0a\uff0a\uff0a\uff0a\uff0a<\/p>\n","protected":false},"excerpt":{"rendered":"

7\/1\u62c5\u5f53\u306e\u4e45\u4fdd\u5065\u4e00\u90ce\uff08\u89e3\u5256\u5b66\u8b1b\u5ea7\uff09\u3067\u3059\u3002 \u5f53\u65e5\u306f\u3001\u4e0b\u8a18\u306e\u8ad6\u6587\u3092\u7d39\u4ecb\u3055\u305b\u3066\u9802\u304f\u4e88\u5b9a\u3067\u3059\u3002 DNA damage burden causes selective CUX2 neuron loss in neuroinfla…<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_jetpack_memberships_contains_paid_content":false,"footnotes":""},"categories":[3],"tags":[],"class_list":["post-600","post","type-post","status-publish","format-standard","hentry","category-journal-club"],"jetpack_sharing_enabled":true,"jetpack_featured_media_url":"","_links":{"self":[{"href":"https:\/\/neuroclub.jikei-neuroscience.com\/index.php?rest_route=\/wp\/v2\/posts\/600","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/neuroclub.jikei-neuroscience.com\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/neuroclub.jikei-neuroscience.com\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/neuroclub.jikei-neuroscience.com\/index.php?rest_route=\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/neuroclub.jikei-neuroscience.com\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=600"}],"version-history":[{"count":0,"href":"https:\/\/neuroclub.jikei-neuroscience.com\/index.php?rest_route=\/wp\/v2\/posts\/600\/revisions"}],"wp:attachment":[{"href":"https:\/\/neuroclub.jikei-neuroscience.com\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=600"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/neuroclub.jikei-neuroscience.com\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=600"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/neuroclub.jikei-neuroscience.com\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=600"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}