Boros Fanni Annamária, Horváth Orsolya, Maszlag-Török Rita, Baranyi Mária, Nánási Nikolett, Oláh-Németh Orsolya, Sperlágh Beáta, Vécsei László, Klivényi Péter
Department of Neurology, Albert Szent-Györgyi Clinical Center, Faculty of Medicine, University of Szeged, Szeged, Hungary.
Department of Molecular Neurology, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg, 91054, Erlangen, Germany.
Sci Rep. 2025 Apr 15;15(1):13027. doi: 10.1038/s41598-025-95787-0.
Parkinson's disease (PD) is the second most common neurodegenerative disease worldwide. Recently long non-coding RNAs (lncRNAs) have emerged as possible molecular hubs in the diverse pathomechanisms of the disease. Among them, NEAT1 gained particular interest due to findings suggesting both protective and deleterious effects of this lncRNA in PD models.The aim of this study was to clarify some of the contradictions among data that appeared in recent publications concerning NEAT1 effects. For this, we determined whether pharmacological increase of NEAT1 levels worsened the detrimental effect of MPP + in the SH-SY5Y cell model, and whether the levels of the short and long isoform of the lncRNA changed differently upon short and extended MPTP treatment in an MPTP-induced mouse model of PD. Our findings suggest differential expression of NEAT1/Neat1 isoforms in MPP + /MPTP-induced PD models, which is in accord with the proposed role of the lncRNA in the general stress response. We propose that first an early up-regulation of Neat1_2 is dominant. The level of Neat1_2 then decreases as pathology progresses, resulting in a shift in the ratio of the two isoforms towards a higher level of Neat1_1 accompanied by damage of the central nervous system.
帕金森病（PD）是全球第二常见的神经退行性疾病。最近，长链非编码RNA（lncRNAs）已成为该疾病多种发病机制中可能的分子枢纽。其中，NEAT1因其在PD模型中的保护和有害作用的研究结果而备受关注。本研究的目的是澄清近期出版物中关于NEAT1作用的数据之间的一些矛盾。为此，我们确定了在SH-SY5Y细胞模型中，NEAT1水平的药理学增加是否会加重MPP +的有害作用，以及在MPTP诱导的PD小鼠模型中，短期和长期MPTP治疗后，lncRNA的短异构体和长异构体水平是否会有不同变化。我们的研究结果表明，在MPP + / MPTP诱导的PD模型中，NEAT1 / Neat1异构体存在差异表达，这与lncRNA在一般应激反应中的作用一致。我们提出，首先是Neat1_2的早期上调占主导。随着病理进展，Neat1_2的水平随后下降，导致两种异构体的比例向更高水平的Neat1_1转变，同时伴有中枢神经系统损伤。
