Department of Pharmacy, Second Xiangya Hospital, Central South University, Changsha, Hunan, China; Institute of Clinical Pharmacy, Second Xiangya Hospital, Central South University, Changsha, Hunan, China; Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, Hunan, China.
Department of Pharmacy, Second Xiangya Hospital, Central South University, Changsha, Hunan, China; Institute of Clinical Pharmacy, Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
Schizophr Res. 2023 Oct;260:12-22. doi: 10.1016/j.schres.2023.07.027. Epub 2023 Aug 3.
Schizophrenia (SZ), a complex and debilitating spectrum of psychiatric disorders, is now mainly attributed to multifactorial etiology that includes genetic and environmental factors. Long non-coding RNAs (lncRNAs) are gaining popularity as a way to better understand the comprehensive mechanisms beneath the clinical manifestation of SZ. Only in recent years has it been elucidated that mammalian genomes encode thousands of lncRNAs. Strikingly, roughly 30-40% of these lncRNAs are extensively expressed in different regions across the brain, which may be closely associated with SZ. The therapeutic and adverse effects of atypical antipsychotic drugs (AAPDs) are partially reflected by their role in the regulation of lncRNAs. This begs the question directly, do any lncRNAs exist as biomarkers for AAPDs treatment? Furthermore, we comprehend a range of mechanistic investigations that have revealed the regulatory roles for lncRNAs both involved in the brain and the periphery of SZ. More crucially, we also combine insights from a variety of signaling pathways to argue that lncRNAs probably play critical roles in SZ via their interactive downstream factors. This review provides a thorough understanding regarding dysregulation of lncRNAs, corresponding genetic alternations, as well as their potential regulatory roles in the pathology of SZ, which might help reveal useful therapeutic targets in SZ.
精神分裂症（SZ）是一种复杂且使人虚弱的精神障碍谱系，其病因主要归因于多因素，包括遗传和环境因素。长链非编码 RNA（lncRNA）作为一种更好地了解 SZ 临床表现背后综合机制的方法，越来越受到关注。直到最近，人们才阐明哺乳动物基因组编码了数千种 lncRNA。引人注目的是，这些 lncRNA 中有大约 30-40%在大脑的不同区域广泛表达，这可能与 SZ 密切相关。非典型抗精神病药物（AAPD）的治疗和不良反应部分反映在它们对 lncRNA 调节的作用上。这就直接提出了一个问题，是否存在任何 lncRNA 作为 AAPD 治疗的生物标志物？此外，我们还理解了一系列机制研究，这些研究揭示了 lncRNA 在 SZ 中的脑内和外周的调节作用。更重要的是，我们还结合了来自各种信号通路的见解，认为 lncRNA 可能通过其相互作用的下游因子在 SZ 中发挥关键作用。这篇综述提供了对 lncRNA 失调、相应的遗传改变以及它们在 SZ 病理学中的潜在调节作用的全面理解，这可能有助于揭示 SZ 中的有用治疗靶点。
