Nature's Immunology has a weighty map of the brain's genes that produce poisons.

Learn about the latest progress in neuroscience ● click on the blue letter to pay attention to us ● oxidative stress (a state of imbalance between oxidation and antioxidation in the body, which tends to oxidize) leads to excessive production of free radicals, which is a negative effect, can lead to cell damage, and is considered to be an important factor leading to aging and disease.these oxidation molecules are collectively referred to as reactive oxygen species (ROS), which play an important role in biological regulation.among them, people are more interested in the fact that oxidative stress can promote the aging of the body. Therefore, some medical and health care products exaggerate the propaganda that anti-oxidation in the body can delay aging, but most of them do not work.studies have shown that ROS mediated oxidative stress released by innate immune cells in the central nervous system promotes neurodegeneration and demyelination.ROS is considered to be a brain toxic substance.on April 13, 2020, the Katerina akassogluu research group of the Weill Institute of neuroscience, University of California, San Francisco, published an article in the journal Nature Immunology, revealing the transcriptome map of oxidative stress in the state of neuroimmune inflammation, and found some targets to inhibit oxidative stress.researchers have developed a technology called tox SEQ, which can only classify and sequence ROS producing neuroimmune cells, and use this single cell sequencing technology to analyze the transcriptome of demyelinating experimental autoimmune encephalitis (EAE) mouse model.this model is usually used as a model of multiple sclerosis due to increased immune response leading to demyelination, axon injury and ultimately motor dysfunction.in fact, tox SEQ can identify two cell groups: one is mainly disease-related, releasing ROS cells CD11b + ROS +, including about 15% microglia and more than 50% monocytes and macrophages and other innate immune cells.the other is that ROS is not released in physiological state, CD11b + ROS cells only include microglia.there are great differences in transcriptomics between the two groups.functional enrichment analysis showed that in EAE model mice, the genes with core oxidative stress signal characteristics were mainly expressed in monocytes and macrophages, and some microglia also showed oxidative stress signal characteristics.P.S. for detailed omics data, you can download the original supplementary materials.although it is divided into many cell groups by transcriptomic characteristics, unlike other transcriptomics analysis, researchers prefer to find targets to inhibit oxidative stress.based on this, they found that the gene network involved in coagulation function and glutathione pathway was co expressed with oxidative stress pathway.what role do these two gene networks play in oxidative stress.fibrin is the final product of the coagulation cascade and is deposited in the brain of patients with multiple sclerosis and Alzheimer's disease. researchers developed a high-throughput technology to screen small molecule inhibitors of oxidative stress, and activated microglia in vitro by activating molecules fibrin and lipopolysaccharide. 1907 compounds were screened by this method, and 128 compounds were found to inhibit the microglial response induced by fibrin or LPS, and 31 compounds were finally identified. it was further found that these compounds were mainly related to the glutathione degrading enzyme gamma glutamyltransferase (GGT) pathway. on the other hand, tox SEQ also found that GGT signaling and oxidative stress related cell groups were enriched and expressed. GGT degrades the antioxidant glutathione, resulting in increased oxidative stress. acivicin, a glutamine analogue and a potent GGT inhibitor, is a chemical substance used in anti-tumor drugs, but its role in inflammatory and neurodegenerative diseases remains unclear. in vitro cell experiments confirmed that asiviscin and ggstop, a GGT inhibitor, could inhibit the activation of microglia induced by fibrin and LPS, increase the level of glutathione, and reduce the production of ROS. more importantly, the dosage of asiviscin has no toxic effect on myeloid cells of peripheral system and neurons of central nervous system. therefore, the researchers further tested the effect of aciviscin on acute and chronic autoimmune neuroinflammation in mice. in EAE model, asivissin and ggstop decreased GGT activity, alleviated neurological symptoms, and mediated T cell response and pro-inflammatory gene expression. in the chronic EAE model treated with aciviscin, the demyelination, axonal injury and oxidative stress were reduced even after 80 days. these results suggest that GGT pathway and ROS play a key role in the development of a wide range of neurodegenerative diseases. in addition, the death of dopaminergic neurons was reduced after aciviscin treatment, which may be due to the reduction of inflammatory response in substantia nigra. these animal disease models jointly emphasize the effective anti-inflammatory and neuroprotective effects of acifertine in neuroinflammatory diseases. in conclusion, this study revealed the transcriptomic characteristics of oxidative stress of innate immune cells in the central nervous system in neuritis by high-throughput sequencing technology, and identified drug targets to inhibit oxidative stress. in addition, the database of transcriptomics related to oxidative stress established a foundation for our study of oxidative stress in inflammatory diseases, which is conducive to further study how diseases are triggered and how diseases develop? Reference: 1. Scriptional profiling and thermal targeting of oxidative stress in neuroinformation2. Don't you know that you're toxseq! Nature Methods: a new technology that can "turn on or off" a single neuron! Nature: stem cell transplantation: a new tool for microglia research! Professor Zhang lining of Shandong University reveals the role of tumor suppressor PDCD4 in depression