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神经元衍生的细胞外囊泡:阿尔茨海默病中新兴的生物标志物和功能介质,并对神经发育和衰老进行比较性洞察

Neuron-Derived Extracellular Vesicles: Emerging Biomarkers and Functional Mediators in Alzheimer's Disease, With Comparative Insights Into Neurodevelopment and Aging.

作者信息

Gonul Ceren Perihan, Karacicek Bilge, Genc Sermin

机构信息

Izmir Biomedicine and Genome Center, Izmir, Turkey.

Izmir International Biomedicine and Genome Institute, Dokuz Eylul University, Izmir, Turkey.

出版信息

Dev Neurobiol. 2025 Jul;85(3):e22984. doi: 10.1002/dneu.22984.

Abstract

Alzheimer's disease (AD) is one of the most common neurodegenerative disorders characterized by the accumulation of amyloid-β (Aβ) peptide and phosphorylated tau protein in the brain. Despite intensive efforts, early diagnosis and monitoring of AD remain challenging due to the lack of reliable biomarkers that can detect the disease in its preclinical stages. As a result, there exists a requirement for novel approaches to the diagnosis and treatment of the disease. Extracellular vesicles provide the transfer of Aβ peptides and tau proteins between the cells and participates in the spreading/propagation of disease pathology. Neuron-derived extracellular vesicles (NDEVs) that are found in plasma have emerged as promising candidates, especially for biomarker studies on neurodegenerative diseases because they are reachable and comparable with cerebrospinal fluid (CSF) studies. In addition to known proteins, synaptic proteins, transcription factors, or microRNAs have been suggested as new biomarkers, aiming to help differential or early diagnosis. Beyond their involvement in AD pathology, NDEVs also play essential roles in neurodevelopment and aging by mediating cell-to-cell communication and regulating processes such as synaptic formation, neuronal differentiation, and neuroinflammation. Age-related alterations in EV composition and secretion may contribute to the decline in neuroplasticity, thereby increasing susceptibility to neurodegenerative diseases like AD. Several challenges such as heterogeneous isolation of NDEVs limit the widespread clinical application of them as biomarkers for AD. Furthermore, the lack of standardized protocols for vesicle isolation and molecular analysis poses a barrier to reproducibility and clinical validation. The aim of this review is to elucidate the role of NDEVs in AD pathogenesis in comparison with their functions in neurodevelopment and aging, evaluate their potential as biomarkers for early diagnosis, while addressing the challenges in their isolation, characterization, and clinical application.

摘要

阿尔茨海默病(AD)是最常见的神经退行性疾病之一,其特征是大脑中淀粉样β(Aβ)肽和磷酸化tau蛋白的积累。尽管付出了巨大努力,但由于缺乏能够在临床前阶段检测该疾病的可靠生物标志物,AD的早期诊断和监测仍然具有挑战性。因此,需要新的疾病诊断和治疗方法。细胞外囊泡介导细胞间Aβ肽和tau蛋白的传递,并参与疾病病理的传播。血浆中发现的神经元衍生细胞外囊泡(NDEVs)已成为有前景的候选物,特别是在神经退行性疾病的生物标志物研究中,因为它们易于获取且可与脑脊液(CSF)研究相媲美。除了已知蛋白质外,突触蛋白、转录因子或微小RNA也被认为是新的生物标志物,旨在帮助进行鉴别诊断或早期诊断。除了参与AD病理过程外,NDEVs还通过介导细胞间通讯和调节突触形成、神经元分化和神经炎症等过程,在神经发育和衰老中发挥重要作用。与年龄相关的细胞外囊泡组成和分泌变化可能导致神经可塑性下降,从而增加患AD等神经退行性疾病的易感性。NDEVs的异质性分离等几个挑战限制了它们作为AD生物标志物的广泛临床应用。此外,缺乏标准化的囊泡分离和分子分析方案对可重复性和临床验证构成了障碍。本综述的目的是阐明NDEVs在AD发病机制中的作用,并与其在神经发育和衰老中的功能进行比较,评估它们作为早期诊断生物标志物的潜力,同时解决其分离、表征和临床应用中的挑战。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d8f4/12160402/4713b418267a/DNEU-85-0-g001.jpg

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