澳大利亚墨尔本大学Justin P. Rubio课题组的研究认为多发性硬化症病变中神经元体细胞突变增多。2025年3月4日，国际知名学术期刊《自然—神经科学》发表了这一成果。

本文研究了10例MS患者和16例对照患者死后脑组织106个神经元基因组中的体细胞单核苷酸变异（sSNVs），以确定体细胞突变是否参与其中。该研究团队观察到，慢性MS病变神经元每年增加43.9个sSNVs，比正常MS和对照组织神经元的速度快2.5倍。这一差异相当于70时病变神经元中sSNVs增加1291个。年龄与对照组相比。该课题组人员进行了突变特征分析，以研究神经元sSNV的机制，并确定了病变的一个特征，该特征对sSNV计数具有强烈的年龄相关贡献。这项研究表明，神经炎症在多发性硬化症大脑中具有诱变性，可能导致疾病进展。

据介绍，神经炎症是多发性硬化症（MS）神经退行性变和临床进展的基础，但有关这些疾病机制的过程的知识仍然不完整。

附：英文原文

Title: Neuronal somatic mutations are increased in multiple sclerosis lesions

Author: Motyer, Allan, Jackson, Stacey, Yang, Bicheng, Harliwong, Ivon, Tian, Wei, Shiu, Wing In Avis, Shao, Yunchang, Wang, Bo, McLean, Catriona, Barnett, Michael, Kilpatrick, Trevor J., Leslie, Stephen, Rubio, Justin P.

Issue&Volume: 2025-03-04

Abstract: Neuroinflammation underpins neurodegeneration and clinical progression in multiple sclerosis (MS), but knowledge of processes linking these disease mechanisms remains incomplete. Here we investigated somatic single-nucleotide variants (sSNVs) in the genomes of 106 single neurons from post-mortem brain tissue of ten MS cases and 16 controls to determine whether somatic mutagenesis is involved. We observed an increase of 43.9 sSNVs per year in neurons from chronic MS lesions, a 2.5 times faster rate than in neurons from normal-appearing MS and control tissues. This difference was equivalent to 1,291 excess sSNVs in lesion neurons at 70years of age compared to controls. We performed mutational signature analysis to investigate mechanisms underlying neuronal sSNVs and identified a signature characteristic of lesions with a strong, age-associated contribution to sSNV counts. This research suggests that neuroinflammation is mutagenic in the MS brain, potentially contributing to disease progression.

DOI: 10.1038/s41593-025-01895-5

Source: https://www.nature.com/articles/s41593-025-01895-5