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精神分裂症:一种由病毒和病原体引起且依赖基因的致病性自身免疫性疾病。

Schizophrenia: a pathogenetic autoimmune disease caused by viruses and pathogens and dependent on genes.

作者信息

Carter C J

机构信息

Polygenic Pathways, 20 Upper Maze Hill, St Leonards-on-Sea, East Sussex, TN38 OLG, UK.

出版信息

J Pathog. 2011;2011:128318. doi: 10.4061/2011/128318. Epub 2011 May 26.

Abstract

Many genes have been implicated in schizophrenia as have viral prenatal or adult infections and toxoplasmosis or Lyme disease. Several autoantigens also target key pathology-related proteins. These factors are interrelated. Susceptibility genes encode for proteins homologous to those of the pathogens while the autoantigens are homologous to pathogens' proteins, suggesting that the risk-promoting effects of genes and risk factors are conditional upon each other, and dependent upon protein matching between pathogen and susceptibility gene products. Pathogens' proteins may act as dummy ligands, decoy receptors, or via interactome interference. Many such proteins are immunogenic suggesting that antibody mediated knockdown of multiple schizophrenia gene products could contribute to the disease, explaining the immune activation in the brain and lymphocytes in schizophrenia, and the preponderance of immune-related gene variants in the schizophrenia genome. Schizophrenia may thus be a "pathogenetic" autoimmune disorder, caused by pathogens, genes, and the immune system acting together, and perhaps preventable by pathogen elimination, or curable by the removal of culpable antibodies and antigens.

摘要

许多基因都与精神分裂症有关,孕期或成人期的病毒感染、弓形虫病或莱姆病也与之相关。几种自身抗原也靶向关键的病理相关蛋白。这些因素相互关联。易感基因编码的蛋白质与病原体的蛋白质同源,而自身抗原与病原体的蛋白质同源,这表明基因和风险因素的促风险作用相互依存,并取决于病原体与易感基因产物之间的蛋白质匹配。病原体的蛋白质可能作为虚拟配体、诱饵受体或通过相互作用组干扰发挥作用。许多此类蛋白质具有免疫原性,这表明抗体介导的多种精神分裂症基因产物的敲低可能导致该病,解释了精神分裂症患者大脑和淋巴细胞中的免疫激活,以及精神分裂症基因组中免疫相关基因变异的优势。因此,精神分裂症可能是一种“致病的”自身免疫性疾病,由病原体、基因和免疫系统共同作用引起,或许可通过消除病原体来预防,或通过去除有问题的抗体和抗原治愈。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ea7/3335463/d6080f7c778e/JPATH2011-128318.001.jpg

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