Department of Neurology, Albert Szent-Györgyi Clinical Center, Faculty of Medicine, University of Szeged, Szeged, Hungary.
MTA-SZTE Neuroscience Research Group of the Hungarian Academy of Sciences and the University of Szeged, Szeged, Hungary.
J Parkinsons Dis. 2021;11(1):123-138. doi: 10.3233/JPD-202374.
Parkinson's disease (PD) is the second most common neurodegenerative disease worldwide. Considering the devastating symptoms, high prevalence, and lack of definitive diagnostic test, there is an urgent need to identify possible biomarkers and new therapeutic targets. Genes identified and/or proposed to be linked to PD encode proteins that fulfill diverse roles in cellular functions. There is a growing interest in identifying common traits which lead to the disease. Long non-coding RNAs have recently emerged as possible regulatory hubs of complex molecular changes affecting PD development. Among them, NEAT1 has attracted particular interest. It is a major component and the initiator of nuclear paraspeckles, thus regulating transcription and modifying protein functions. This review summarizes data available on the role of NEAT1 in PD. NEAT1 upregulation in PD has repeatedly been reported, however, whether this is part of a protective or a damaging mechanism is still a topic of debate. It has been proposed that NEAT1 propagates PD via its interaction with PINK1 and several micro RNAs and by modulating SNCA expression. On the other hand, findings of NEAT1 acting as a bona fide LRRK2 inhibitor argue for its protective role. These contradictory results could be due to the different disease models implemented. This calls attention to the difficulties posed by the complex patho-mechanisms of neurodegenerative disorders and the limitations of disease models. However, the potential of NEAT1 as a biomarker and as a therapeutic target for PD highly warrants further research to elucidate its exact role in this neurodegenerative disorder.
帕金森病（PD）是全球第二常见的神经退行性疾病。鉴于其毁灭性的症状、高发病率以及缺乏明确的诊断测试，因此迫切需要确定可能的生物标志物和新的治疗靶点。已确定和/或提出与 PD 相关的基因编码在细胞功能中发挥多种作用的蛋白质。人们越来越关注识别导致疾病的常见特征。长非编码 RNA 最近已成为影响 PD 发展的复杂分子变化的可能调节中心。其中，NEAT1 引起了特别的关注。它是核斑的主要组成部分和启动子，从而调节转录并修饰蛋白质功能。这篇综述总结了有关 NEAT1 在 PD 中的作用的数据。已有报道称 PD 中 NEAT1 的上调，但这是否是保护机制还是破坏机制的一部分仍存在争议。据报道，NEAT1 通过与 PINK1 和几种 microRNAs 的相互作用以及调节 SNCA 表达来传播 PD。另一方面，发现 NEAT1 作为 LRRK2 的有效抑制剂，证明其具有保护作用。这些相互矛盾的结果可能是由于实施了不同的疾病模型。这引起了对神经退行性疾病复杂病理机制和疾病模型局限性的关注。然而，NEAT1 作为 PD 的生物标志物和治疗靶点具有很高的研究价值，需要进一步研究来阐明其在这种神经退行性疾病中的确切作用。
