Department of Biomedical Sciences and Pathobiology, Virginia Tech, Blacksburg, VA 24061, USA.
Virginia Tech Carilion School of Medicine, Roanoke, VA 24016, USA.
Cells. 2022 Oct 25;11(21):3364. doi: 10.3390/cells11213364.
Neurological disorders are highly prevalent and often lead to chronic debilitating disease. Neuroinflammation is a major driver across the spectrum of disorders, and microglia are key mediators of this response, gaining wide acceptance as a druggable cell target. Moreover, clinical providers have limited ability to objectively quantify patient-specific changes in microglia status, which can be a predictor of illness and recovery. This necessitates the development of diagnostic biomarkers and imaging techniques to monitor microglia-mediated neuroinflammation in coordination with neurological outcomes. New insights into the polarization status of microglia have shed light on the regulation of disease progression and helped identify a modifiable target for therapeutics. Thus, the detection and monitoring of microglia activation through the inclusion of diagnostic biomarkers and imaging techniques will provide clinical tools to aid our understanding of the neurologic sequelae and improve long-term clinical care for patients. Recent achievements demonstrated by pre-clinical studies, using novel depletion and cell-targeted approaches as well as single-cell RNAseq, underscore the mechanistic players that coordinate microglial activation status and offer a future avenue for therapeutic intervention.
神经紊乱高度普遍，并常导致慢性衰弱性疾病。神经炎症是各种疾病的主要驱动因素，小胶质细胞是这种反应的关键介质，作为可药物治疗的细胞靶点得到了广泛认可。此外，临床医生客观量化患者小胶质细胞状态特定变化的能力有限，而这种变化可能是疾病和恢复的预测指标。因此，需要开发诊断生物标志物和成像技术，以与神经学结果协调监测小胶质细胞介导的神经炎症。对小胶质细胞极化状态的新认识揭示了疾病进展的调控，并有助于确定治疗的可调节靶点。因此，通过纳入诊断生物标志物和成像技术来检测和监测小胶质细胞的激活，将为临床提供工具，以帮助我们了解神经后遗症，并改善患者的长期临床护理。临床前研究取得的最新进展表明，使用新型耗竭和细胞靶向方法以及单细胞 RNAseq，可以协调小胶质细胞激活状态的机制参与者，并为治疗干预提供未来途径。
