Role of pattern recognition receptors and the microbiota in neurological disorders.
Role of pattern recognition receptors and the microbiota in neurological disorders.
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模式识别受体和微生物区系在神经疾病中的作用。
DOI：
10.1113/jp279771
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发表时间：
2021-03
期刊：
影响因子：
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通讯作者：
Gareau MG
中科院分区：
文献类型：
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作者：
Keogh CE;Rude KM;Gareau MG
近年来，肠道微生物群越来越多地参与许多肠外疾病的发展，包括神经发育和神经退行性疾病。尽管这种联系越来越多，但我们目前对这些影响背后的确切机制缺乏了解。模式识别受体（PRR）是重要的先天免疫蛋白，其表达在多种细胞（免疫细胞和其他细胞，包括上皮细胞、内皮细胞和神经元细胞）的表面上和细胞质内。PRR包括四个主要的亚家族：Toll样受体（TLR）、核苷酸结合寡聚化结构域富含亮氨酸重复序列的受体（NLR）、视黄酸诱导基因1样受体和C型凝集素受体。PRR对肠道细菌的识别对于维持宿主-微生物相互作用和稳态（包括行为）至关重要。PRR在多种细胞类型上的表达使其成为调节宿主-微生物信号传导的高度有趣和新颖的靶标，这可能导致肠-脑信号传导。新出现的证据表明，四个已知的PRR家族中的两个（NLR和TLR）通过肠-脑轴参与神经发育和神经退行性疾病的发病机制。总之，越来越多的证据支持这些PRR通过微生物群-肠-脑轴在神经系统疾病（包括阿尔茨海默病、帕金森病和多发性硬化症）的发展中的作用。微生物群-肠-脑（MGB）轴参与脑中疾病（包括神经发育和神经变性病症）和肠道疾病（包括炎性肠病）的发病机制。模式识别受体（PRR）如TLR和NLR参与这些复杂的肠-脑疾病的发展，部分通过肠道微生物群的生态失调和免疫应答的改变。
In recent years, the gut microbiota has been increasingly implicated in the development of many extraintestinal disorders, including neurodevelopmental and neurodegenerative disorders. Despite this growing connection, our understanding of the precise mechanisms behind these effects is currently lacking. Pattern recognition receptors (PRRs) are important innate immune proteins expressed on the surface and within the cytoplasm of a multitude of cells, both immune and otherwise, including epithelial, endothelial and neuronal. PRRs comprise four major subfamilies: the Toll-like receptors (TLRs), the nucleotide-binding oligomerization domain leucine rich repeats-containing receptors (NLRs), the retinoic acid inducible gene 1-like receptors and the C-type lectin receptors. Recognition of commensal bacteria by PRRs is critical for maintaining host–microbe interactions and homeostasis, including behaviour. The expression of PRRs on multiple cell types makes them a highly interesting and novel target for regulation of host–microbe signalling, which may lead to gut–brain signalling. Emerging evidence indicates that two of the four known families of PRRs (the NLRs and the TLRs) are involved in the pathogenesis of neurodevelopmental and neurodegenerative disorders via the gut–brain axis. Taken together, increasing evidence supports a role for these PRRs in the development of neurological disorders, including Alzheimer’s disease, Parkinson’s disease and multiple sclerosis, via the microbiota–gut–brain axis. The microbiota-gut-brain (MGB) axis is involved in the pathogenesis of diseases both in the brain, including neurodevelopmental and neurodegenerative disorders, and diseases of the gut, including inflammatory bowel diseases. Pattern recognition receptors (PRRs) such as TLRs and NLRs are implicated in the development of these complex gut-brain disorders, in part via dysbiosis of the gut microbiota and alterations in the immune response.