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靶向尿酸:一种针对神经退行性疾病中氧化应激和神经炎症的有前景的干预措施。

Targeting uric acid: a promising intervention against oxidative stress and neuroinflammation in neurodegenerative diseases.

作者信息

Xu Lin, Li Chengwei, Wan Tiantian, Sun Xinyi, Lin Xiaojie, Yan Dong, Li Jianjun, Wei Penghui

机构信息

Department of Anesthesiology, Cheeloo College of Medicine, Qilu Hospital (Qingdao), Shandong University, 758 Hefei Road, Qingdao, China.

Laboratory of Anesthesia and Brain Function, Qilu hospital (Qingdao), Cheeloo College of Medicine, Shandong University, 758 Hefei Road, Qingdao, China.

出版信息

Cell Commun Signal. 2025 Jan 3;23(1):4. doi: 10.1186/s12964-024-01965-4.

Abstract

Oxidative stress and neuroinflammation are recognized as key factors in the development of neurodegenerative diseases, yet effective interventions and biomarkers to address oxidative stress and neuroinflammation in these conditions are limited. Uric acid (UA), traditionally associated with gout, is now gaining prominence as a potential target in neurodegenerative diseases. Soluble UA stands out as one of the most vital antioxidant compounds produced by the human body, accounting for up to 55% of the extracellular capacity to neutralize free radicals. While there is increasing evidence supporting the neuroprotective properties of UA in Parkinson's disease and Alzheimer's disease, gaps in knowledge still exist regarding the underlying mechanisms and how to effectively translate these benefits into clinical practice. Moreover, the current UA elevation therapy exhibits unstable antioxidant properties, individual variability, and even adverse effects, limiting its potential clinical applications. This review consolidates recent advancements in understanding how UA exerts neuroprotective effects on neurodegenerative diseases and emphasizes the dual roles of UA in managing oxidative stress and neuroinflammation. Additionally, the review elucidates the mechanisms through which UA confers neuroprotection. Based on this, the review underscores the significance of UA as a potential biomarker and aims to provide a comprehensive understanding of its potential as a therapeutic target, while also addressing possible challenges to clinical implementation.

摘要

氧化应激和神经炎症被认为是神经退行性疾病发展的关键因素,但针对这些情况下的氧化应激和神经炎症的有效干预措施和生物标志物却很有限。尿酸(UA)传统上与痛风相关,现在作为神经退行性疾病的潜在靶点正日益受到关注。可溶性尿酸是人体产生的最重要的抗氧化化合物之一,占细胞外中和自由基能力的55%。虽然越来越多的证据支持尿酸在帕金森病和阿尔茨海默病中的神经保护特性,但在其潜在机制以及如何将这些益处有效转化为临床实践方面,仍存在知识空白。此外,目前的尿酸升高疗法表现出不稳定的抗氧化特性、个体差异甚至不良反应,限制了其潜在的临床应用。本综述总结了最近在理解尿酸如何对神经退行性疾病发挥神经保护作用方面的进展,并强调了尿酸在管理氧化应激和神经炎症方面的双重作用。此外,该综述阐明了尿酸赋予神经保护作用的机制。基于此,该综述强调了尿酸作为潜在生物标志物的重要性,旨在全面了解其作为治疗靶点的潜力,同时也应对临床实施中可能面临的挑战。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da2c/11699683/eeb70eafe57a/12964_2024_1965_Fig1_HTML.jpg

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