Molecular Pharmacology & Toxicology Laboratory, Department of Biotechnology, School of Life Sciences, Central University of Tamil Nadu, Neelakudi Campus, Thiruvarur, 610005, India.
Department of Basic Medical Sciences, College of Medicine, Prince Sattam Bin Abdulaziz University, Al-Kharj, 11942, Kingdom of Saudi Arabia.
Mol Neurobiol. 2024 Jul;61(7):4619-4632. doi: 10.1007/s12035-023-03809-7. Epub 2023 Dec 18.
Parkinson's disease (PD) is one of the complex neurodegenerative disorders, primarily characterized by motor deficits, including bradykinesia, tremor, rigidity, and postural instability. The underlying pathophysiology involves the progressive loss of dopaminergic neurons within the substantia nigra pars compacta, leading to dopamine depletion in the basal ganglia circuitry. While motor symptoms are hallmark features of PD, emerging research highlights a wide range of non-motor symptoms, including cognitive impairments, mood disturbances, and autonomic dysfunctions. Inflammasome activation is pivotal in inducing neuroinflammation and promoting disease onset, progression, and severity of PD. Several studies have shown that long noncoding RNAs (lncRNAs) modulate inflammasomes in the pathogenesis of neurodegenerative diseases. Dysregulation of lncRNAs is linked to aberrant gene expression and cellular processes in neurodegeneration, causing the activation of inflammasomes that contribute to neuroinflammation and neurodegeneration. Inflammasomes are cytosolic proteins that form complexes upon activation, inducing inflammation and neuronal cell death. This review explores the significance of lncRNAs in regulating inflammasomes in PD, primarily focusing on specific lncRNAs such as nuclear paraspeckle assembly transcript 1 (NEATNEAT1), X-inactive specific transcript (XIST), growth arrest-specific 5 (GAS5), and HOX transcript antisense RNA (HOTAIR), which have been shown to activate or inhibit the NLRP3 inflammasome and induce the release of proinflammatory cytokines. Moreover, some lncRNAs mediate inflammasome activation through miRNA interactions. Understanding the roles of lncRNAs in inflammasome regulation provides new therapeutic targets for controlling neuroinflammation and reducing the progression of neurodegeneration. Identifying lncRNA-mediated regulatory pathways paves the way for novel therapies in the battle against these devastating neurodegenerative disorders.
帕金森病（PD）是一种复杂的神经退行性疾病，主要表现为运动缺陷，包括运动迟缓、震颤、僵硬和姿势不稳。其潜在的病理生理学涉及黑质致密部多巴胺能神经元的进行性丧失，导致基底节回路中多巴胺耗竭。虽然运动症状是 PD 的标志性特征，但新兴研究强调了广泛的非运动症状，包括认知障碍、情绪障碍和自主功能障碍。炎性小体的激活在诱导神经炎症和促进 PD 的发病、进展和严重程度中起着关键作用。多项研究表明，长非编码 RNA（lncRNA）在神经退行性疾病的炎性小体发病机制中起调节作用。lncRNA 的失调与神经退行性变中异常基因表达和细胞过程有关，导致炎性小体的激活，从而导致神经炎症和神经退行性变。炎性小体是细胞溶质蛋白，在激活时形成复合物，诱导炎症和神经元细胞死亡。本综述探讨了 lncRNA 在 PD 中调节炎性小体的重要性，主要集中在特定的 lncRNA 上，如核小体组装转录物 1（NEAT1）、X 染色体失活特异转录物（XIST）、生长停滞特异性 5（GAS5）和 HOX 转录反义 RNA（HOTAIR），它们已被证明可激活或抑制 NLRP3 炎性小体并诱导促炎细胞因子的释放。此外，一些 lncRNA 通过 miRNA 相互作用介导炎性小体的激活。了解 lncRNA 在炎性小体调节中的作用为控制神经炎症和减少神经退行性变的进展提供了新的治疗靶点。鉴定 lncRNA 介导的调节途径为对抗这些破坏性神经退行性疾病开辟了新的治疗途径。
