Human Endogenous Retrovirus K in Astrocytes Is Altered in Parkinson's Disease.

IF 7.4 1区医学 Q1 CLINICAL NEUROLOGY Movement Disorders Pub Date : 2025-01-22 DOI:10.1002/mds.30128

YuHong Fu, Gabrielle L Adler, Priscilla Youssef, Katherine Phan, Glenda M Halliday, Nicolas Dzamko, Woojin Scott Kim

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Abstract

Background: Parkinson's disease (PD) is the most common neurodegenerative movement disease. Human endogenous retroviruses (HERVs) are proviral remnants of ancient retroviral infection of germ cells that now constitute about 8% of the human genome. Under certain disease conditions, HERV genes are activated and partake in the disease process. However, virtually nothing is known about the pathological relationship, if any, between HERV and PD.

Objective: The objectives of this study were to unravel the pathological relationship between human endogenous retrovirus K (HERV-K) and PD, determine the localization of HERV-K in the brain, determine whether HERV-K levels are altered in PD brain and blood, and examine whether HERV-K could serve as a biomarker for PD.

Methods: In situ HERV-K and glial fibrillary acidic protein (GFAP) expression in the superior frontal and fusiform cortices of PD and control brain were analyzed using immunofluorescence and confocal microscopy. HERV-K load and copy number in PD and control blood were measured by digital droplet polymerase chain reaction and GFAP by single-molecule array. HERV-K load was analyzed in relation to the Hoehn and Yahr Scale and Movement Disorder Society Unified Parkinson's Disease Rating Scale Part III.

Results: HERV-K is predominantly expressed in astrocytes and colocalized with astrocytic GFAP, with decreased expression of both HERV-K and GFAP in PD brain compared with controls. Consistent with this, HERV-K levels were decreased in PD blood compared with controls and were correlated to blood GFAP levels. HERV-K levels were inversely correlated to PD severity and duration.

Conclusions: These findings suggest that HERV-K is related to astrocyte function and to PD progression, and that HERV-K could be neuroprotective. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

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人类星形胶质细胞内源性逆转录病毒K在帕金森病中发生改变

背景：帕金森病（PD）是最常见的神经退行性运动疾病。人类内源性逆转录病毒（herv）是古老的生殖细胞逆转录病毒感染的前病毒残余物，现在约占人类基因组的8%。在某些疾病条件下，HERV基因被激活并参与疾病过程。然而，几乎没有人知道HERV和PD之间的病理关系，如果有的话。目的：本研究旨在揭示人内源性逆转录病毒K （HERV-K）与PD的病理关系，确定HERV-K在脑中的定位，确定HERV-K在PD脑和血液中的水平是否发生改变，并探讨HERV-K是否可以作为PD的生物标志物。方法：应用免疫荧光和共聚焦显微镜分析PD和对照脑额叶上皮层和梭状回皮层中HERV-K和胶质纤维酸性蛋白（GFAP）的原位表达。采用数字液滴聚合酶链反应和单分子阵列GFAP检测PD和对照血中HERV-K的载量和拷贝数。HERV-K负荷与Hoehn and Yahr量表和运动障碍学会统一帕金森病评定量表第三部分的关系进行分析。结果：HERV-K主要在星形胶质细胞中表达，与星形胶质细胞GFAP共定位，与对照组相比，PD脑中HERV-K和GFAP的表达均降低。与此一致的是，与对照组相比，PD血液中的HERV-K水平降低，并与血液GFAP水平相关。HERV-K水平与PD的严重程度和持续时间呈负相关。结论：这些发现提示HERV-K与星形细胞功能和PD进展有关，并且HERV-K可能具有神经保护作用。©2025作者。Wiley期刊有限责任公司代表国际帕金森和运动障碍学会出版的《运动障碍》。

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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.