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帕金森病中,外周血单个核细胞线粒体功能与T细胞细胞因子相关。

Peripheral Mononuclear Cell Mitochondrial Function Associates with T-Cell Cytokines in Parkinson's Disease.

作者信息

Afaar Fatima, Youssef Priscilla, Galper Jasmin, Chua Michelle, Halliday Glenda M, Lewis Simon J G, Dzamko Nicolas

机构信息

School of Medical Sciences, Faculty of Medicine and Health and the Brain and Mind Centre, University of Sydney, Camperdown, Australia.

Parkinson's Disease Research Clinic, Macquarie Medical School, Macquarie University, Sydney, Australia.

出版信息

Mov Disord. 2025 Aug;40(8):1625-1635. doi: 10.1002/mds.30233. Epub 2025 May 16.

DOI:10.1002/mds.30233
PMID:40377205
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12371616/
Abstract

BACKGROUND

Parkinson's disease (PD) is the most common neurodegenerative movement disorder and one of the world's fastest-growing neurological diseases. Although the exact causes of PD are unknown, mitochondrial dysfunction and inflammation may have significant roles in disease progression. As well as being prevalent in the brain, there is also evidence that peripheral mitochondrial dysfunction and inflammation occur in PD. However, if/how peripheral mitochondrial dysfunction and inflammation are linked is still unclear.

OBJECTIVES

This study aimed to determine the extent that mitochondrial dysfunction in peripheral immune cells is associated with inflammation in PD.

METHODS

The study comprised of 35 controls and 35 PD patients that were age and sex matched. Flow cytometry was used to assess mitochondrial content and superoxide production in mononuclear cells, in the presence and absence of the mitochondrial stressor antimycin A. Serum inflammatory cytokines were measured by ELISA.

RESULTS

Superoxide levels were significantly increased in PD patient mononuclear cells at baseline, and PD mononuclear cells had an impaired response to antimycin A. Immune cell superoxide levels correlated with serum cytokines associated with T-cell responses, namely interleukin (IL) IL-12, interferon-γ, and IL-17A.

CONCLUSIONS

Results show that mitochondrial dysfunction is prevalent in PD immune cells and may contribute to an inflammatory phenotype. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

摘要

背景

帕金森病(PD)是最常见的神经退行性运动障碍疾病,也是全球增长最快的神经疾病之一。尽管PD的确切病因尚不清楚,但线粒体功能障碍和炎症可能在疾病进展中起重要作用。除了在大脑中普遍存在外,也有证据表明PD患者存在外周线粒体功能障碍和炎症。然而,外周线粒体功能障碍与炎症之间是否存在关联以及如何关联仍不清楚。

目的

本研究旨在确定外周免疫细胞中的线粒体功能障碍与PD炎症的关联程度。

方法

该研究纳入了35名年龄和性别匹配的对照者以及35名PD患者。使用流式细胞术评估单核细胞中线粒体含量和超氧化物生成情况,分别在存在和不存在线粒体应激剂抗霉素A的情况下进行检测。通过酶联免疫吸附测定法(ELISA)检测血清炎症细胞因子。

结果

PD患者单核细胞在基线时超氧化物水平显著升高,且PD单核细胞对抗霉素A的反应受损。免疫细胞超氧化物水平与与T细胞反应相关的血清细胞因子,即白细胞介素(IL)-12、干扰素-γ和IL-17A相关。

结论

结果表明线粒体功能障碍在PD免疫细胞中普遍存在,并可能导致炎症表型。© 2025作者。《运动障碍》由威利期刊有限责任公司代表国际帕金森和运动障碍协会出版。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0823/12371616/a39b59e80c32/MDS-40-1625-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0823/12371616/7e1436afa393/MDS-40-1625-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0823/12371616/44fd7ba1e7f0/MDS-40-1625-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0823/12371616/a39b59e80c32/MDS-40-1625-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0823/12371616/7e1436afa393/MDS-40-1625-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0823/12371616/44fd7ba1e7f0/MDS-40-1625-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0823/12371616/a39b59e80c32/MDS-40-1625-g003.jpg

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本文引用的文献

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IL-2/anti-IL-2 complexes attenuates neuroinflammation and neurodegeneration in mice of experimental Parkinson's disease.白细胞介素-2/抗白细胞介素-2复合物可减轻实验性帕金森病小鼠的神经炎症和神经退行性变。
Brain Res Bull. 2025 Apr;223:111273. doi: 10.1016/j.brainresbull.2025.111273. Epub 2025 Feb 23.
2
The impact of anti-inflammatory therapy on Parkinson's disease incidence: A retrospective cohort study.抗炎治疗对帕金森病发病率的影响:一项回顾性队列研究。
Parkinsonism Relat Disord. 2025 Jan;130:107194. doi: 10.1016/j.parkreldis.2024.107194. Epub 2024 Nov 7.
3
Single-cell peripheral immunoprofiling of lewy body and Parkinson's disease in a multi-site cohort.
多中心队列中单细胞外周免疫谱分析路易体和帕金森病。
Mol Neurodegener. 2024 Aug 1;19(1):59. doi: 10.1186/s13024-024-00748-2.
4
Interleukin-2 expands neuroprotective regulatory T cells in Parkinson's disease.白细胞介素-2可扩增帕金森病中的神经保护性调节性T细胞。
NeuroImmune Pharm Ther. 2022 Jun 21;1(1):43-50. doi: 10.1515/nipt-2022-0001. eCollection 2022 Mar.
5
Multimodal assessment of mitochondrial function in Parkinson's disease.帕金森病中线粒体功能的多模态评估。
Brain. 2024 Jan 4;147(1):267-280. doi: 10.1093/brain/awad364.
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Cytokine activity in Parkinson's disease.帕金森病中的细胞因子活性。
Neuronal Signal. 2023 Dec 4;7(4):NS20220063. doi: 10.1042/NS20220063. eCollection 2023 Dec.
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