小柯机器人

英国牛津大学Lars Fugger课题组鉴定了进展性多发性硬化症（MS）的早期神经退行性通路。2022年6月20日出版的《自然-神经科学》杂志发表了这项成果。

研究人员对新鲜冷冻的人MS脑组织进行了空间转录组学和蛋白质组学研究，确定了导致进展性MS发病的多细胞机制，并追踪其与神经退行性变空间分布阶段相关的起源。通过解析局部微环境中的配体-受体相互作用，研究发现早期神经元衰退区域内的营养和抗炎细胞间通讯丢失，患者样本中与神经元损伤相关蛋白质具有与已发表的体内敲低和中枢神经系统(CNS)疾病模型一致的表型，表明它们具有作为进展性MS治疗潜在靶点的价值。

该研究结果为药物研发提供了一个新思路，其基于对人类患病组织中促进这种衰弱性疾病复杂细胞和信号动力学的理解。

据悉，进展性多发性硬化症的特征是持续性神经退行性变，这会导致累积性残疾并且对目前的治疗无响应。研发预防该疾病进展的药物具有紧迫的临床需求，但受到对其复杂发病机制研究有限的限制。

附：英文原文

Title: Identification of early neurodegenerative pathways in progressive multiple sclerosis

Author: Kaufmann, Max, Schaupp, Anna-Lena, Sun, Rosa, Coscia, Fabian, Dendrou, Calliope A., Cortes, Adrian, Kaur, Gurman, Evans, Hayley G., Mollbrink, Annelie, Navarro, Jos Fernndez, Sonner, Jana K., Mayer, Christina, DeLuca, Gabriele C., Lundeberg, Joakim, Matthews, Paul M., Attfield, Kathrine E., Friese, Manuel A., Mann, Matthias, Fugger, Lars

Issue&Volume: 2022-06-20

Abstract: Progressive multiple sclerosis (MS) is characterized by unrelenting neurodegeneration, which causes cumulative disability and is refractory to current treatments. Drug development to prevent disease progression is an urgent clinical need yet is constrained by an incomplete understanding of its complex pathogenesis. Using spatial transcriptomics and proteomics on fresh-frozen human MS brain tissue, we identified multicellular mechanisms of progressive MS pathogenesis and traced their origin in relation to spatially distributed stages of neurodegeneration. By resolving ligand–receptor interactions in local microenvironments, we discovered defunct trophic and anti-inflammatory intercellular communications within areas of early neuronal decline. Proteins associated with neuronal damage in patient samples showed mechanistic concordance with published in vivo knockdown and central nervous system (CNS) disease models, supporting their causal role and value as potential therapeutic targets in progressive MS. Our findings provide a new framework for drug development strategies, rooted in an understanding of the complex cellular and signaling dynamics in human diseased tissue that facilitate this debilitating disease.

DOI: 10.1038/s41593-022-01097-3

Source: https://www.nature.com/articles/s41593-022-01097-3

Nature Neuroscience：《自然—神经科学》，创刊于1998年。隶属于施普林格·自然出版集团，最新IF：28.771
官方网址：https://www.nature.com/neuro/
投稿链接：https://mts-nn.nature.com/cgi-bin/main.plex