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非编码 RNA 作为帕金森病炎症发病机制的调节因子的机制观点。

The mechanistic view of non-coding RNAs as a regulator of inflammatory pathogenesis of Parkinson's disease.

机构信息

Department of Neurosurgery, Jilin Province FAW General Hospital, Changchun 130000, China.

Department of Neurosurgery, Jilin Province FAW General Hospital, Changchun 130000, China.

出版信息

Pathol Res Pract. 2024 Jun;258:155349. doi: 10.1016/j.prp.2024.155349. Epub 2024 May 16.

Abstract

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta, leading to motor and non-motor symptoms. Emerging evidence suggests that inflammation plays a crucial role in the pathogenesis of PD, with the NLRP3 inflammasome implicated as a key mediator. Nfon-coding RNAs (ncRNAs), including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), have recently garnered attention for their regulatory roles in various biological processes, including inflammation. This review aims to provide a mechanistic insight into how ncRNAs function as regulators of inflammatory pathways in PD, with a specific focus on the NLRP3 inflammasome. We discuss the dysregulation of miRNAs and lncRNAs in PD pathogenesis and their impact on neuroinflammation through modulation of NLRP3 activation, cytokine production, and microglial activation. Additionally, we explore the crosstalk between ncRNAs, alpha-synuclein pathology, and mitochondrial dysfunction, further elucidating the intricate network underlying PD-associated inflammation. Understanding the mechanistic roles of ncRNAs in regulating inflammatory pathways may offer novel therapeutic targets for the treatment of PD and provide insights into the broader implications of ncRNA-mediated regulation in neuroinflammatory diseases.

摘要

帕金森病(PD)是一种神经退行性疾病,其特征是黑质致密部多巴胺能神经元进行性丧失,导致运动和非运动症状。新出现的证据表明,炎症在 PD 的发病机制中起着关键作用,NLRP3 炎性小体被认为是关键的介导者。非编码 RNA(ncRNA),包括 microRNAs(miRNAs)和长非编码 RNA(lncRNAs),最近因其在包括炎症在内的各种生物学过程中的调节作用而受到关注。本综述旨在深入了解 ncRNA 如何作为 PD 中炎症途径的调节剂发挥作用,特别关注 NLRP3 炎性小体。我们讨论了 miRNAs 和 lncRNAs 在 PD 发病机制中的失调及其通过调节 NLRP3 激活、细胞因子产生和小胶质细胞激活对神经炎症的影响。此外,我们还探讨了 ncRNA 与α-突触核蛋白病理学和线粒体功能障碍之间的串扰,进一步阐明了 PD 相关炎症背后复杂的网络。了解 ncRNA 在调节炎症途径中的机制作用可能为 PD 的治疗提供新的治疗靶点,并深入了解 ncRNA 介导的调节在神经炎症性疾病中的广泛意义。

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