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神经系统失调的 microRNAs:在帕金森病发病机制和生物标志物开发中的意义。

Dysregulated microRNAs in neural system: Implication in pathogenesis and biomarker development in Parkinson's disease.

机构信息

School of Life Science, Beijing Institute of Technology, No 5 South Zhongguancun Street, Haidian District, Beijing 100081, PR China.

School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, PR China.

出版信息

Neuroscience. 2017 Dec 4;365:70-82. doi: 10.1016/j.neuroscience.2017.09.033. Epub 2017 Sep 28.

Abstract

Parkinson's disease is a debilitating neurodegenerative movement disorder, characterized by the progressive and selective loss of dopaminergic neurons located in the substantia nigra, leading to clinical motor symptoms. The factors involved in PD are rather multifaceted. There are many cellular pathways contributing to its neuro-pathogenesis, which include abnormal protein aggregation, impaired ubiquitin proteasome system, autophagy, and neuroinflammation. However, despite years of investigation, still little is known about early events in the molecular pathogenesis. MicroRNAs are small non-coding RNAs that can regulate post-transcriptional expression of mRNAs. Since they somewhat modulate many mRNA targets simultaneously, many cellular pathways may be affected by one individual miRNA. Moreover, miRNAs can stably circulate in cerebrospinal fluid and blood, and their expression pattern can reflect the molecular pathophysiology, thus making them promising biomarkers in PD diagnosis and prognosis. In this review, we will review the recent progress on miRNA's mechanism in PD pathogenesis and discuss the possibilities of miRNAs as PD molecular biomarkers.

摘要

帕金森病是一种使人虚弱的神经退行性运动障碍,其特征是位于黑质中的多巴胺能神经元进行性和选择性丧失,导致临床运动症状。参与 PD 的因素相当复杂。有许多细胞途径有助于其神经发病机制,包括异常蛋白质聚集、泛素蛋白酶体系统受损、自噬和神经炎症。然而,尽管经过多年的研究,对分子发病机制的早期事件仍知之甚少。微小 RNA 是一种小的非编码 RNA,可以调节 mRNA 的转录后表达。由于它们同时在一定程度上调节许多 mRNA 靶标,因此许多细胞途径可能受到一个单个 miRNA 的影响。此外,miRNA 可以稳定地在脑脊液和血液中循环,其表达模式可以反映分子病理生理学,因此使它们成为 PD 诊断和预后的有前途的生物标志物。在这篇综述中,我们将回顾 miRNA 在 PD 发病机制中的作用的最新进展,并讨论 miRNA 作为 PD 分子生物标志物的可能性。

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