From blood vessels to brain cells: Connecting the circulatory system and Parkinson's disease.

IF 4 3区 医学 Q2 NEUROSCIENCES
Journal of Parkinson's disease Pub Date : 2025-03-01 Epub Date: 2025-01-29 DOI:10.1177/1877718X241308168
Oyedele J Olaoye, Sophie L Farrow, Denis M Nyaga, Antony A Cooper, Justin M O'Sullivan
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引用次数: 0

Abstract

Parkinson's disease (PD) is traditionally recognized as a neurodegenerative disorder characterized by motor dysfunction and α-synuclein protein accumulation in the brain. However, recent research suggests that the circulatory system may also contribute to PD pathogenesis through the spread of α-synuclein beyond the brain. The blood-brain barrier (BBB), a key regulator of molecular exchange between the bloodstream and the brain, may become compromised in PD, allowing harmful substances, including pathogenic forms of α-synuclein, to infiltrate the brain and promote neurodegeneration. Transport mechanisms such as P-glycoprotein and the low-density lipoprotein (LDL) receptor-related protein (LRP-1) further modulate the movement of α-synuclein across the BBB, influencing disease progression. Additionally, extracellular vesicles are emerging as crucial mediators in the dissemination of α-synuclein between the brain and peripheral tissues, facilitating its spread and accumulation. The lymphatic system, responsible for clearing α-synuclein, may also contribute to PD pathology when impaired. This review highlights the growing evidence for a circulatory axis in the initiation and progression of PD. We propose that future research should explore the hypothesis that the circulatory system contributes to the pathogenesis of PD by aiding the distribution of α-synuclein throughout the body.

从血管到脑细胞:循环系统与帕金森病的联系。
帕金森病(PD)传统上被认为是一种以运动功能障碍和大脑α-突触核蛋白积累为特征的神经退行性疾病。然而,最近的研究表明,循环系统也可能通过α-突触核蛋白在脑外的扩散参与PD的发病机制。血脑屏障(BBB)是血液和大脑之间分子交换的关键调节因子,可能在PD中受损,使有害物质,包括致病形式的α-突触核蛋白,渗入大脑并促进神经退行性变。转运机制如p -糖蛋白和低密度脂蛋白受体相关蛋白(LRP-1)进一步调节α-突触核蛋白在血脑屏障上的运动,影响疾病进展。此外,细胞外囊泡作为α-突触核蛋白在脑和外周组织之间传播的重要介质,促进其扩散和积累。负责清除α-突触核蛋白的淋巴系统在受损时也可能导致PD病理。这篇综述强调了越来越多的证据表明循环轴在PD的发生和发展中起作用。我们建议未来的研究应该探索循环系统通过帮助α-突触核蛋白在全身的分布而参与PD发病机制的假设。
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
CiteScore
8.40
自引率
5.80%
发文量
338
审稿时长
>12 weeks
期刊介绍: The Journal of Parkinson''s Disease (JPD) publishes original research in basic science, translational research and clinical medicine in Parkinson’s disease in cooperation with the Journal of Alzheimer''s Disease. It features a first class Editorial Board and provides rigorous peer review and rapid online publication.
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