Brain-derived extracellular vesicles: A promising avenue for Parkinson's disease pathogenesis, diagnosis, and treatment.

IF 5.9 2区 医学 Q2 CELL BIOLOGY
Neural Regeneration Research Pub Date : 2026-04-01 Epub Date: 2025-04-29 DOI:10.4103/NRR.NRR-D-24-01262
Shurui Zhang, Jingwen Li, Xinyu Hu, Hanshu Liu, Qinwei Yu, Guiying Kuang, Long Liu, Danfang Yu, Zhicheng Lin, Nian Xiong
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引用次数: 0

Abstract

The misfolding, aggregation, and deposition of alpha-synuclein into Lewy bodies are pivotal events that trigger pathological changes in Parkinson's disease. Extracellular vesicles are nanosized lipid-bilayer vesicles secreted by cells that play a crucial role in intercellular communication due to their diverse cargo. Among these, brain-derived extracellular vesicles, which are secreted by various brain cells such as neurons, glial cells, and Schwann cells, have garnered increasing attention. They serve as a promising tool for elucidating Parkinson's disease pathogenesis and for advancing diagnostic and therapeutic strategies. This review highlights the recent advancements in our understanding of brain-derived extracellular vesicles released into the blood and their role in the pathogenesis of Parkinson's disease, with specific emphasis on their involvement in the aggregation and spread of alpha-synuclein. Brain-derived extracellular vesicles contribute to disease progression through multiple mechanisms, including autophagy-lysosome dysfunction, neuroinflammation, and oxidative stress, collectively driving neurodegeneration in Parkinson's disease. Their application in Parkinson's disease diagnosis is a primary focus of this review. Recent studies have demonstrated that brain-derived extracellular vesicles can be isolated from peripheral blood samples, as they carry α-synuclein and other key biomarkers such as DJ-1 and various microRNAs. These findings highlight the potential of brain-derived extracellular vesicles, not only for the early diagnosis of Parkinson's disease but also for disease progression monitoring and differential diagnosis. Additionally, an overview of explorations into the potential therapeutic applications of brain-derived extracellular vesicles for Parkinson's disease is provided. Therapeutic strategies targeting brain-derived extracellular vesicles involve modulating the release and uptake of pathological alpha-synuclein -containing brain-derived extracellular vesicles to inhibit the spread of the protein. Moreover, brain-derived extracellular vesicles show immense promise as therapeutic delivery vehicles capable of transporting drugs into the central nervous system. Importantly, brain-derived extracellular vesicles also play a crucial role in neural regeneration by promoting neuronal protection, supporting axonal regeneration, and facilitating myelin repair, further enhancing their therapeutic potential in Parkinson's disease and other neurological disorders. Further clarification is needed of the methods for identifying and extracting brain-derived extracellular vesicles, and large-scale cohort studies are necessary to validate the accuracy and specificity of these biomarkers. Future research should focus on systematically elucidating the unique mechanistic roles of brain-derived extracellular vesicles, as well as their distinct advantages in the clinical translation of methods for early detection and therapeutic development.

脑源性细胞外囊泡:帕金森病发病机制、诊断和治疗的一个有希望的途径。
摘要/ Abstract摘要:α -突触核蛋白在路易小体中的错误折叠、聚集和沉积是引发帕金森病病理变化的关键事件。细胞外囊泡是由细胞分泌的纳米级脂质双层囊泡,由于其载物的多样性,在细胞间通讯中起着至关重要的作用。其中,由神经元、神经胶质细胞、雪旺细胞等多种脑细胞分泌的脑源性细胞外囊泡受到了越来越多的关注。它们是阐明帕金森病发病机制和推进诊断和治疗策略的有前途的工具。本文综述了脑源性细胞外囊泡释放到血液中的最新进展及其在帕金森病发病机制中的作用,特别强调了它们参与α -突触核蛋白的聚集和扩散。脑源性细胞外囊泡通过多种机制促进疾病进展,包括自噬-溶酶体功能障碍、神经炎症和氧化应激,共同驱动帕金森病的神经变性。它们在帕金森病诊断中的应用是本综述的主要重点。最近的研究表明,脑源性细胞外囊泡可以从外周血样本中分离出来,因为它们携带α-突触核蛋白和其他关键生物标志物,如DJ-1和各种microrna。这些发现强调了脑源性细胞外囊泡的潜力,不仅可以用于帕金森病的早期诊断,还可以用于疾病进展监测和鉴别诊断。此外,还概述了脑源性细胞外囊泡对帕金森病的潜在治疗应用的探索。针对脑源性细胞外囊泡的治疗策略包括调节病理性含有α -突触核蛋白的脑源性细胞外囊泡的释放和摄取,以抑制该蛋白的扩散。此外,脑源性细胞外囊泡作为能够将药物运送到中枢神经系统的治疗递送载体显示出巨大的前景。重要的是,脑源性细胞外囊泡还通过促进神经元保护、支持轴突再生和促进髓鞘修复在神经再生中发挥重要作用,进一步增强了其在帕金森病和其他神经系统疾病中的治疗潜力。识别和提取脑源性细胞外囊泡的方法需要进一步澄清,需要大规模队列研究来验证这些生物标志物的准确性和特异性。未来的研究应侧重于系统地阐明脑源性细胞外囊泡的独特机制作用,以及它们在早期发现和治疗开发方法的临床翻译中的独特优势。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Neural Regeneration Research
Neural Regeneration Research CELL BIOLOGY-NEUROSCIENCES
CiteScore
8.00
自引率
9.80%
发文量
515
审稿时长
1.0 months
期刊介绍: Neural Regeneration Research (NRR) is the Open Access journal specializing in neural regeneration and indexed by SCI-E and PubMed. The journal is committed to publishing articles on basic pathobiology of injury, repair and protection to the nervous system, while considering preclinical and clinical trials targeted at improving traumatically injuried patients and patients with neurodegenerative diseases.
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