7/1担当の久保健一郎（解剖学講座）です。
当日は、下記の論文を紹介させて頂く予定です。
DNA damage burden causes selective CUX2 neuron loss in neuroinflammation
Nature. 2026 May;653(8115):809-818. doi: 10.1038/s41586-026-10310-3. Epub 2026 Apr 1.
PMID: 41922773
PMCID: PMC13190333
DOI: 10.1038/s41586-026-10310-3
Abstract；
Neurodegeneration 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-γ, 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.
以下のlinkより、Open accessの論文です。
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どうぞよろしくお願い致します。
久保健一郎
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東京慈恵会医科大学解剖学講座
〒105-8461 東京都港区西新橋３丁目２５番８号
内線：2206 Tel：03-3433-1111（大代表）
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kennykubo
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