Arias-Carrión Oscar, Reyes-Mata María Paulina, Zúñiga Joaquín, Ortuño-Sahagún Daniel
División de Neurociencias|Clínica, Instituto Nacional de Rehabilitación Luis Guillermo Ibarra Ibarra, Mexico City 14389, Mexico.
Tecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Mexico City 14380, Mexico.
Brain Sci. 2025 Jul 16;15(7):756. doi: 10.3390/brainsci15070756.
Parkinson's disease (PD) is a progressive neurodegenerative disorder marked by dopaminergic neuronal loss, α-synuclein aggregation, and chronic neuroinflammation. Recent evidence suggests that exosomal microRNAs (miRNAs)-small, non-coding RNAs encapsulated in extracellular vesicles-are key regulators of PD pathophysiology and promising candidates for biomarker development and therapeutic intervention. Exosomes facilitate intercellular communication, cross the blood-brain barrier, and protect miRNAs from degradation, rendering them suitable for non-invasive diagnostics and targeted delivery. Specific exosomal miRNAs modulate neuroinflammatory cascades, oxidative stress, and synaptic dysfunction, and their altered expression in cerebrospinal fluid and plasma correlates with disease onset, severity, and progression. Despite their translational promise, challenges persist, including methodological variability in exosome isolation, miRNA profiling, and delivery strategies. This review integrates findings from preclinical models, patient-derived samples, and systems biology to delineate the functional impact of exosomal miRNAs in PD. We propose mechanistic hypotheses linking miRNA dysregulation to molecular pathogenesis and present an interactome model highlighting therapeutic nodes. Advancing exosomal miRNA research may transform the clinical management of PD by enabling earlier diagnosis, molecular stratification, and the development of disease-modifying therapies.
帕金森病（PD）是一种进行性神经退行性疾病，其特征为多巴胺能神经元丧失、α-突触核蛋白聚集和慢性神经炎症。最近的证据表明，外泌体微小RNA（miRNA）——封装在细胞外囊泡中的小的非编码RNA——是PD病理生理学的关键调节因子，也是生物标志物开发和治疗干预的有前景的候选物。外泌体促进细胞间通讯，穿过血脑屏障，并保护miRNA不被降解，使其适用于非侵入性诊断和靶向递送。特定的外泌体miRNA调节神经炎症级联反应、氧化应激和突触功能障碍，它们在脑脊液和血浆中的表达改变与疾病的发作、严重程度和进展相关。尽管它们具有转化应用前景，但挑战依然存在，包括外泌体分离、miRNA分析和递送策略方面的方法学差异。本综述整合了临床前模型、患者来源样本和系统生物学的研究结果，以阐明外泌体miRNA在PD中的功能影响。我们提出了将miRNA失调与分子发病机制联系起来的机制假说，并提出了一个突出治疗节点的相互作用组模型。推进外泌体miRNA研究可能会通过实现早期诊断、分子分层和开发疾病修饰疗法来改变PD的临床管理。
