Plasma Glucosylceramide Levels Are Regulated by ATP10D and Are Not Involved in Parkinson's Disease Pathogenesis.

IF 8.1 1区医学 Q1 CLINICAL NEUROLOGY

Annals of Neurology Pub Date : 2025-03-01 DOI:10.1002/ana.27219

Emma N Somerville, Alva James, Christian Beetz, Robert Schwieger, Gal Barrel, Krishna K Kandaswamy, Marius I Iurascu, Peter Bauer, Michael Ta, Hirotaka Iwaki, Konstantin Senkevich, Eric Yu, Roy N Alcalay, Ziv Gan-Or

引用次数: 0

Abstract

GBA1 variants and decreased glucocerebrosidase activity are implicated in Parkinson's disease (PD). We investigated the hypothesis that increased levels of glucosylceramide (GlcCer), a main substrate of glucocerebrosidase, are involved in PD pathogenesis. Using multiple genetic methods, we show that ATPase phospholipid transporting 10D (ATP10D), not GBA1, is the main regulator of plasma GlcCer levels, yet it is not involved in PD pathogenesis. Plasma GlcCer levels were associated with PD, but not in a causative manner, and are not predictive of disease status. These results argue against targeting GlcCer in GBA1-PD, and underscore the need to explore alternative mechanisms and biomarkers for PD. ANN NEUROL 2025.

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血浆葡萄糖甘油三酯水平受 ATP10D 调节，与帕金森病发病机制无关

GBA1变体和葡萄糖脑苷脂酶活性降低与帕金森病（PD）有关。我们研究了葡萄糖脑苷脂酶的主要底物--葡萄糖酰甘油酰胺（GlcCer）水平升高与帕金森病发病机制有关的假说。通过多种遗传学方法，我们发现ATP酶磷脂转运10D（ATP10D）而非GBA1是血浆GlcCer水平的主要调节因子，但它与帕金森病的发病机制无关。血浆 GlcCer 水平与帕金森病有关，但不是致病因素，也不能预测疾病状态。这些结果反对以GBA1-PD中的GlcCer为靶点，并强调了探索PD替代机制和生物标志物的必要性。ann neurol 2025.

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

Annals of Neurology 医学-临床神经学

CiteScore

18.00

自引率

1.80%

发文量

270

审稿时长

3-8 weeks

期刊介绍： Annals of Neurology publishes original articles with potential for high impact in understanding the pathogenesis, clinical and laboratory features, diagnosis, treatment, outcomes and science underlying diseases of the human nervous system. Articles should ideally be of broad interest to the academic neurological community rather than solely to subspecialists in a particular field. Studies involving experimental model system, including those in cell and organ cultures and animals, of direct translational relevance to the understanding of neurological disease are also encouraged.