Huang Zhonghua, Zhao Jing, Wang Wei, Zhou Jun, Zhang Jie
Department of Neurology, The Second Xiangya Hospital, Central South University, Changsha, China.
Medical Science Research Center, Xiangya Hospital, Central South University, Changsha, China.
Front Cell Neurosci. 2020 Feb 19;14:28. doi: 10.3389/fncel.2020.00028. eCollection 2020.
Alzheimer's disease (AD) is the most common neurodegenerative disorder and the main cause of dementia among the elderly worldwide. Unfortunately, the mechanism of AD remains unclear, and no effective therapies are available yet. An increasing amount of studies have demonstrated that long non-coding RNAs (LncRNAs) play a notable role in the pathogenesis of plenty of human diseases, and they have served as biomarkers and potential therapeutic targets. However, the function of LncRNAs in AD remains unclear. This study aimed to explore the potential role of LncRNA nuclear enriched abundant transcript 1 (NEAT1) in AD. We found that LncRNA NEAT1 was upregulated in the AD animal models. Furthermore, we demonstrated that NEAT1 could interact with NEDD4L and promote PTEN-induced putative kinase 1 (PINK1)'s ubiquitination and degradation and then impaired PINK1-dependent autophagy. Collectively, the lncRNA NEAT1 promotes the pathogenesis of AD and serves as a promising novel target for pharmacological intervention.
阿尔茨海默病（AD）是全球最常见的神经退行性疾病，也是老年人痴呆的主要病因。遗憾的是，AD的发病机制仍不清楚，目前尚无有效的治疗方法。越来越多的研究表明，长链非编码RNA（LncRNAs）在多种人类疾病的发病机制中发挥着显著作用，它们已成为生物标志物和潜在的治疗靶点。然而，LncRNAs在AD中的功能仍不清楚。本研究旨在探讨长链非编码RNA核富集丰富转录本1（NEAT1）在AD中的潜在作用。我们发现，在AD动物模型中LncRNA NEAT1表达上调。此外，我们证明NEAT1可以与NEDD4L相互作用，促进PTEN诱导的假定激酶1（PINK1）的泛素化和降解，进而损害PINK1依赖的自噬。总的来说，lncRNA NEAT1促进了AD的发病机制，是一个有前景的新型药物干预靶点。
