小柯机器人

美国格拉德斯通研究所Katerina Akassoglou小组的一项最新研究，通过转录谱分析揭示了靶向氧化应激的神经炎症治疗。这一研究成果于2020年4月13日发表在《自然— 免疫学》上。

研究人员揭示了神经炎性疾病中产生氧化应激先天免疫细胞的转录图谱，并发现了新的可药物化途径。通过对中枢神经系统中产生氧化应激的先天免疫细胞进行转录谱分析，研究人员确定了核心氧化应激基因的特点，即小胶质细胞簇和浸润性巨噬细胞之间共享的凝血和谷胱甘肽途径相偶联。

先进行Tox-seq，然后进行小胶质细胞高通量筛选和氧化应激基因网络分析，研究人员发现在慢性和复发性多发性硬化症模型中，谷胱甘肽调节化合物阿西维汀可以有效地降低氧化应激和轴突损伤。因此，通过氧化应激转录组学，可以发现具有神经毒性的中枢神经系统先天免疫人群，并可能促进开发选择性的神经保护机制。

研究人员表示，氧化应激是先天免疫诱导神经退行性病变的主要原因。但是，尚不清楚中枢神经系统中导致氧化应激先天免疫细胞的转录组情况，并且尚不存在针对其神经毒性的治疗。

附：英文原文

Title: Transcriptional profiling and therapeutic targeting of oxidative stress in neuroinflammation

Author: Andrew S. Mendiola, Jae Kyu Ryu, Sophia Bardehle, Anke Meyer-Franke, Kenny Kean-Hooi Ang, Chris Wilson, Kim M. Baeten, Kristina Hanspers, Mario Merlini, Sean Thomas, Mark A. Petersen, Alexander Williams, Reuben Thomas, Victoria A. Rafalski, Rosa Meza-Acevedo, Reshmi Tognatta, Zhaoqi Yan, Samuel J. Pfaff, Michael R. Machado, Catherine Bedard, Pamela E. Rios Coronado, Xiqian Jiang, Jin Wang, Michael A. Pleiss, Ari J. Green, Scott S. Zamvil, Alexander R. Pico, Benoit G. Bruneau, Michelle R. Arkin, Katerina Akassoglou

Issue&Volume: 2020-04-13

Abstract: Oxidative stress is a central part of innate immune-induced neurodegeneration. However, the transcriptomic landscape of central nervous system (CNS) innate immune cells contributing to oxidative stress is unknown, and therapies to target their neurotoxic functions are not widely available. Here, we provide the oxidative stress innate immune cell atlas in neuroinflammatory disease and report the discovery of new druggable pathways. Transcriptional profiling of oxidative stress–producing CNS innate immune cells identified a core oxidative stress gene signature coupled to coagulation and glutathione-pathway genes shared between a microglia cluster and infiltrating macrophages. Tox-seq followed by a microglia high-throughput screen and oxidative stress gene network analysis identified the glutathione-regulating compound acivicin, with potent therapeutic effects that decrease oxidative stress and axonal damage in chronic and relapsing multiple sclerosis models. Thus, oxidative stress transcriptomics identified neurotoxic CNS innate immune populations and may enable discovery of selective neuroprotective strategies.

DOI: 10.1038/s41590-020-0654-0

Source: https://www.nature.com/articles/s41590-020-0654-0

Nature Immunology：《自然—免疫学》，创刊于2000年。隶属于施普林格·自然出版集团，最新IF：31.25
官方网址：https://www.nature.com/ni/
投稿链接：https://mts-ni.nature.com/cgi-bin/main.plex