Abstract

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.

中文翻译：

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NEAT1 论帕金森病领域：进攻、防守还是替补球员？

 抽象的

帕金森病（PD）是全球第二常见的神经退行性疾病。考虑到其严重的症状、高患病率以及缺乏明确的诊断测试，迫切需要确定可能的生物标志物和新的治疗靶点。已鉴定和/或提议与 PD 相关的基因编码在细胞功能中发挥不同作用的蛋白质。人们对识别导致该疾病的共同特征越来越感兴趣。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尤其引起了人们的兴趣。它是核副斑的主要成分和引发剂，从而调节转录和修饰蛋白质功能。本综述总结了有关 NEAT1 在 PD 中的作用的可用数据。 NEAT1 在 PD 中的上调已多次被报道，然而，这是保护性机制还是破坏性机制的一部分仍然是一个争论的话题。有人提出，NEAT1通过与 PINK1 和几种 micro RNA 相互作用以及调节SNCA表达来传播 PD。另一方面，NEAT1 作为真正的 LRRK2 抑制剂的发现证明了其保护作用。这些矛盾的结果可能是由于所采用的疾病模型不同所致。这引起了人们对神经退行性疾病复杂病理机制和疾病模型局限性所带来的困难的关注。然而，NEAT1 作为 PD 生物标志物和治疗靶点的潜力非常值得进一步研究，以阐明其在这种神经退行性疾病中的确切作用。