Centre for Global Health Research, Saveetha Medical College, Saveetha Institute of Medical and Technical Sciences, India.
Department of Pharmaceutics, College of Pharmacy, Prince Sattam bin Abdulaziz University, Alkharj 11942, Saudi Arabia.
Pathol Res Pract. 2024 Sep;261:155511. doi: 10.1016/j.prp.2024.155511. Epub 2024 Jul 30.
Parkinson's disease is one of the vital neurodegenerative ailments attributed to a rise in Alpha-synuclein proteins leading to the advancement of motor and cognitive deterioration. Interestingly, in PD lncRNAs, miRNAs and siRNAs are also key regulators of SNCA and alpha-synuclein aggregation. This review will focus on the roles of these three types of small RNAs in trebling the development of PD through regulating SNCA expression or alpha-synuclein protein mediating the RNA from acting. Parkinson's disease is defined by the build-up of alpha-synuclein protein resulting predominantly from the elevated expression level of the SNCA gene. Non-coding RNAs have gained broad appeal as fundamental modulators of gene expression and protein aggregation dynamics, with significant implications on the aetiology of PD. LncRNAs modulate SNCA transcription and edit epigenetic modifications, while miRNA target mRNA is involved in the stability and translation of count alpha-synuclein. Considering all these data, siRNAs can achieve the precise gene silencing effect that directly induces the downregulation of SNCA mRNA. This review also summarizes some recent reports about the interaction between these ncRNAs with the SNCA gene and alpha-synuclein protein, each through its independent in addition to synergistic mechanisms. This review highlights the possibility of therapeutic interventions to perturb SNCA expression to prevent alpha-synuclein aggregation via targeting ncRNAs that might be spun off novel drug development for PD.
帕金森病是一种重要的神经退行性疾病，其发病机制与α-突触核蛋白的积累有关，导致运动和认知功能的进行性恶化。有趣的是，在帕金森病中，长链非编码 RNA、微小 RNA 和 siRNA 也是 SNCA 和α-突触核蛋白聚集的关键调节因子。本综述将重点讨论这三种类型的小分子 RNA 通过调节 SNCA 表达或α-突触核蛋白介导 RNA 作用来增加帕金森病发展的作用。帕金森病是由α-突触核蛋白的积累引起的，主要是由于 SNCA 基因的表达水平升高。非编码 RNA 作为基因表达和蛋白质聚集动力学的基本调节剂，已经引起了广泛的关注，对帕金森病的发病机制有重要影响。长链非编码 RNA 调节 SNCA 的转录和编辑表观遗传修饰，而 miRNA 靶向 mRNA 参与计数α-突触核蛋白的稳定性和翻译。考虑到所有这些数据，siRNA 可以实现精确的基因沉默效果，直接下调 SNCA mRNA 的表达。本综述还总结了一些关于这些 ncRNA 与 SNCA 基因和α-突触核蛋白相互作用的最新报告，每种 ncRNA 都通过其独立的和协同的机制发挥作用。本综述强调了通过靶向可能扰乱 SNCA 表达的 ncRNA 来预防α-突触核蛋白聚集的治疗干预的可能性，这可能为帕金森病开发新的药物提供了一种可能。
