Immunometabolic Signature and Tauopathy Markers in Blood Cells of Progressive Supranuclear Palsy.

IF 7.4 1区医学 Q1 CLINICAL NEUROLOGY

Movement Disorders Pub Date : 2024-09-16 DOI:10.1002/mds.30009

Marco Rosina, Federica Veltri, Valentina Nesci, Jacopo Bissacco, Roberta Bovenzi, Davide Mascioli, Clara Simonetta, Henri Zenuni, Daniela Maftei, Massimo Marano, Mariangela Pierantozzi, Alessandro Stefani, Valerio Chiurchiù, Patrizia Longone, Cristiana Valle, Nicola Biagio Mercuri, Alberto Ferri, Tommaso Schirinzi

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引用次数: 0

Abstract

Background: Peripheral immune cells critically contribute to the clinical-pathological progression of neurodegenerative diseases and also represent a reliable frame for translational applications. However, data on progressive supranuclear palsy (PSP) are almost scarce in this regard.

Objective: Our goal is to provide a broad biological characterization of peripheral immune cells in a selected PSP cohort.

Methods: Seventy-one PSP patients scored on the PSP Rating Scale (PSPRS), and 59 controls were enrolled. The blood cell count was collected, together with the neutrophil-to-lymphocyte ratio (NLR) calculation. In a subgroup of patients and controls, the peripheral blood mononuclear cells (PBMCs) were analyzed by the mitochondrial bioenergetic performance and the western blot assay of the nuclear factor erythroid 2-related factor (NRF2)/heme oxygenase 1 (HO-1) pathway and the total tau (t-tau) and phosphorylated tau (p-tau) proteins. Case-control comparison and correlation analyses were performed.

Results: PSP patients had a NLR higher than controls, with increased circulating neutrophils. The leukocyte metabolism was also globally increased and the NRF2/HO-1 pathway activated in patients. P-tau, but not t-tau, significantly accumulated in PSP PBMCs and inversely correlated with the PSPRS.

Conclusions: PSP displays a systemic inflammatory shift of the peripheral immunity, which may justify a metabolic reprogramming of the blood leukocytes. Consistently, the NRF2/HO-1 pathway, a master regulator of inflammatory and metabolic response, was activated. PBMCs also engulf tau proteins, especially p-tau, in a way inverse to the disease severity, allowing for a peripheral tracking of tauopathy in patients. Immunometabolic targets may, therefore, gain relevance to PSP in biomarker or therapeutic purposes. © 2024 International Parkinson and Movement Disorder Society.

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进行性核上性麻痹血细胞中的免疫代谢特征和 Tauopathy 标记物

背景：外周免疫细胞对神经退行性疾病的临床病理进展起着至关重要的作用，同时也是转化应用的可靠框架。然而，有关进行性核上性麻痹（PSP）的这方面数据几乎是稀缺的：我们的目标是对选定的 PSP 患者群的外周免疫细胞进行广泛的生物学特征描述：方法：我们招募了 71 名根据 PSP 评定量表（PSPRS）评分的 PSP 患者和 59 名对照组患者。收集血细胞计数并计算中性粒细胞与淋巴细胞比率（NLR）。在一组患者和对照组中，对外周血单核细胞（PBMCs）进行了线粒体生物能分析，并对核因子红细胞2相关因子（NRF2）/血红素加氧酶1（HO-1）通路以及总tau（t-tau）和磷酸化tau（p-tau）蛋白进行了Western印迹检测。进行了病例对照比较和相关性分析：结果：PSP 患者的 NLR 高于对照组，循环中性粒细胞增加。患者的白细胞新陈代谢也全面增加，NRF2/HO-1通路被激活。P-tau 而非 t-tau 在 PSP PBMCs 中明显累积，并与 PSPRS 成反比：结论：PSP 表现出外周免疫系统的系统性炎症转变，这可能是血液白细胞代谢重编程的原因。NRF2/HO-1 通路是炎症和新陈代谢反应的主要调节因子，它也被激活了。白细胞介导细胞还能吞噬 tau 蛋白，尤其是 p-tau，其吞噬方式与疾病的严重程度成反比，从而能对患者的 tau 病变进行外周追踪。因此，免疫代谢目标可能与帕金森病的生物标记或治疗目的相关。© 2024 国际帕金森病和运动障碍协会。

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来源期刊

Movement Disorders 医学-临床神经学

CiteScore

13.30

自引率

8.10%

发文量

371

审稿时长

12 months

期刊介绍： Movement Disorders publishes a variety of content types including Reviews, Viewpoints, Full Length Articles, Historical Reports, Brief Reports, and Letters. The journal considers original manuscripts on topics related to the diagnosis, therapeutics, pharmacology, biochemistry, physiology, etiology, genetics, and epidemiology of movement disorders. Appropriate topics include Parkinsonism, Chorea, Tremors, Dystonia, Myoclonus, Tics, Tardive Dyskinesia, Spasticity, and Ataxia.