Neuroscience Research Australia, Randwick, NSW, 2031, Australia.
School of Psychiatry, University of New South Wales, Randwick, NSW, 2031, Australia.
Transl Psychiatry. 2021 Oct 14;11(1):528. doi: 10.1038/s41398-021-01607-0.
Neuroinflammation, particularly in the dorsolateral prefrontal cortex, is well-established in a subset of people with schizophrenia, with significant increases in inflammatory markers including several cytokines. Yet the cause(s) of cortical inflammation in schizophrenia remains unknown. Clues as to potential microenvironmental triggers and/or intracellular deficits in immunoregulation may be gleaned from looking further upstream of effector immune molecules to transcription factors that control inflammatory gene expression. Here, we focus on the 'master immune regulator' nuclear factor kappa B (NF-κB) and review evidence in support of NF-κB dysregulation causing or contributing to neuroinflammation in patients. We discuss the utility of 'immune biotyping' as a tool to analyse immune-related transcripts and proteins in patient tissue, and the insights into cortical NF-κB in schizophrenia revealed by immune biotyping compared to studies treating patients as a single, homogenous group. Though the ubiquitous nature of NF-κB presents several hurdles for drug development, targeting this key immunoregulator with novel or repurposed therapeutics in schizophrenia is a relatively underexplored area that could aid in reducing symptoms of patients with active neuroinflammation.
神经炎症，特别是在精神分裂症患者的背外侧前额叶皮层中，已经得到了充分证实，炎症标志物包括几种细胞因子显著增加。然而，精神分裂症患者皮质炎症的原因仍不清楚。从效应免疫分子的上游，即控制炎症基因表达的转录因子，寻找潜在的微环境触发因素和/或细胞内免疫调节缺陷的线索，可能有助于揭示这一问题。在这里，我们重点关注“主免疫调节因子”核因子 kappa B（NF-κB），并回顾支持 NF-κB 失调导致或促成患者神经炎症的证据。我们讨论了“免疫分型”作为一种分析患者组织中免疫相关转录本和蛋白的工具的实用性，以及与将患者视为单一、同质群体进行治疗的研究相比，免疫分型揭示的精神分裂症患者皮质 NF-κB 的见解。尽管 NF-κB 的普遍存在给药物开发带来了几个障碍，但针对这种关键免疫调节剂，用新型或再利用的治疗方法治疗精神分裂症是一个相对未被充分探索的领域，可能有助于减轻有活性神经炎症的患者的症状。
Zotero 插件
