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大脑中的低语:神经病理学中的细胞外囊泡与神经疾病的诊断奥秘

Whispers in the Brain: Extracellular Vesicles in Neuropathology and the Diagnostic Alchemy of Neurological Diseases.

作者信息

Isik Melis, Sari Hatice Kubra, Caglayan Mehmet Gokhan, Yilmaz Rezzak, Derkus Burak

机构信息

Stem Cell Research Lab, Department of Chemistry, Faculty of Science, Ankara University, Ankara, Turkey.

Department of Neurology, School of Medicine, Ankara University, Ankara, Turkey.

出版信息

Eur J Neurosci. 2025 Apr;61(8):e70090. doi: 10.1111/ejn.70090.

Abstract

Extracellular vesicles (EVs) have emerged as pivotal mediators in neurological diseases, showcasing multifaceted potential roles ranging from pathogenesis to diagnosis. These nano-sized membranous structures, released by various cell types including neurons, astrocytes, and microglia, encapsulate a diverse cargo of proteins, lipids, RNA species, and even DNA fragments. In neuropathology, EVs contribute significantly to intercellular communication within the central nervous system (CNS), influencing physiological or pathological cascades. Through the transfer of bioactive molecules, EVs modulate neuroinflammation, neuronal survival, synaptic plasticity, and the propagation of protein aggregates characteristic of neurodegenerative disorders. Moreover, their presence in biofluids such as cerebrospinal fluid (CSF), blood, and urine reflects the pathophysiological state of the CNS, offering a window into the diagnosis, monitoring and treatment of neurological diseases. Recent advancements in EV isolation techniques, coupled with high-throughput omics technologies, have facilitated the profiling of EV cargo, enabling the identification of disease-specific biomarkers with high sensitivity and specificity. This review explores the intricate roles of EVs in neuropathology, highlighting their involvement in Alzheimer's disease, Parkinson's disease, multiple sclerosis, and other neurological disorders. Furthermore, it delves into the diagnostic potential of EVs, discussing current challenges and prospects in harnessing EV-derived biomarkers for precision medicine in neurology. Ultimately, understanding the biology of EVs in neurological contexts promises transformative insights into disease mechanisms and therapeutic strategies, paving the way for innovative diagnostic tools and targeted interventions in clinical practice.

摘要

细胞外囊泡(EVs)已成为神经疾病中的关键介质,展现出从发病机制到诊断的多方面潜在作用。这些纳米级的膜结构由包括神经元、星形胶质细胞和小胶质细胞在内的各种细胞类型释放,包裹着蛋白质、脂质、RNA种类甚至DNA片段等多种物质。在神经病理学中,EVs对中枢神经系统(CNS)内的细胞间通讯有显著贡献,影响生理或病理级联反应。通过生物活性分子的转移,EVs调节神经炎症、神经元存活、突触可塑性以及神经退行性疾病特征性蛋白质聚集体的传播。此外,它们在脑脊液(CSF)、血液和尿液等生物流体中的存在反映了CNS的病理生理状态,为神经疾病的诊断、监测和治疗提供了一个窗口。EV分离技术的最新进展,加上高通量组学技术,促进了对EV所载物质的分析,能够以高灵敏度和特异性识别疾病特异性生物标志物。这篇综述探讨了EVs在神经病理学中的复杂作用,强调了它们在阿尔茨海默病、帕金森病、多发性硬化症和其他神经疾病中的参与。此外,它还深入研究了EVs的诊断潜力,讨论了在利用EV衍生的生物标志物用于神经学精准医学方面当前面临的挑战和前景。最终,了解神经环境中EVs的生物学特性有望为疾病机制和治疗策略带来变革性的见解,为临床实践中的创新诊断工具和靶向干预铺平道路。

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