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

IF 4 3区 医学 Q2 NEUROSCIENCES
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.

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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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