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微小RNA:中枢神经系统疾病中微胶质细胞和星形胶质细胞介导的炎症的关键参与者。

MicroRNAs: Key Players in Microglia and Astrocyte Mediated Inflammation in CNS Pathologies.

作者信息

Karthikeyan Aparna, Patnala Radhika, Jadhav Shweta P, Eng-Ang Ling, Dheen S Thameem

机构信息

Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, MD10, 4 Medical Drive, Singapore 117594.

出版信息

Curr Med Chem. 2016;23(30):3528-3546. doi: 10.2174/0929867323666160814001040.

Abstract

The significance of microglia and astrocytes in neural development, in maintaining synaptic connections and homeostasis in the healthy brain is well established. Microglia are dynamic immune cells of the brain that elicit an immune response during brain damage and also participate in tissue repair and regeneration, while astrocytes contribute to the local inflammatory response by producing proinflammatory cytokines and resolving neuronal damage through production of anti-inflammatory cytokines and neurotrophic factors. Recent efforts have focused on elucidating the epigenetic mechanisms which regulate glial cell behavior in normal and pathologic states. An important class of epigenetic regulators is microRNAs (miRNAs) which are small non-coding RNA molecules that regulate gene expression posttranscriptionally. Certain dysregulated miRNAs contribute to chronic microglial inflammation in the brain, thereby leading to progression of neurological diseases like Alzheimer's disease, traumatic injury, amyotrophic lateral sclerosis and stroke. Further, several miRNAs are differentially expressed in astrocytes after ischemia and spinal cord injury. Despite knowledge about miRNAs in neuroinflammation, little is known about effective delivery routes and pharmacokinetic data for miRNA based therapeutics. This review summarizes the current research on the role of miRNAs in promoting and inhibiting inflammatory response of microglia and astrocytes in a disease-specific manner. In addition, miRNA delivery as a therapeutic strategy to treat neuroinflammation is discussed.

摘要

小胶质细胞和星形胶质细胞在神经发育、维持健康大脑中的突触连接和内环境稳定方面的重要性已得到充分证实。小胶质细胞是大脑中的动态免疫细胞,在脑损伤时引发免疫反应,并参与组织修复和再生,而星形胶质细胞通过产生促炎细胞因子促进局部炎症反应,并通过产生抗炎细胞因子和神经营养因子来解决神经元损伤。最近的研究致力于阐明在正常和病理状态下调节胶质细胞行为的表观遗传机制。一类重要的表观遗传调节因子是微小RNA(miRNA),它们是小的非编码RNA分子,在转录后调节基因表达。某些失调的miRNA会导致大脑中的慢性小胶质细胞炎症,从而导致阿尔茨海默病、创伤性损伤、肌萎缩侧索硬化症和中风等神经疾病的进展。此外,在缺血和脊髓损伤后,星形胶质细胞中有几种miRNA的表达存在差异。尽管对神经炎症中的miRNA有所了解,但对于基于miRNA的治疗方法的有效递送途径和药代动力学数据知之甚少。本综述总结了目前关于miRNA以疾病特异性方式促进和抑制小胶质细胞和星形胶质细胞炎症反应作用的研究。此外,还讨论了将miRNA递送作为治疗神经炎症的一种治疗策略。

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