Prospective Role of PAK6 and 14-3-3γ as Biomarkers for Parkinson’s Disease

IF 4 3区医学 Q2 NEUROSCIENCES Journal of Parkinson's disease Pub Date : 2024-04-23 DOI:10.3233/jpd-230402

Elena Giusto, Lorenza Maistrello, Lucia Iannotta, Veronica Giusti, Ludovica Iovino, Rina Bandopadhyay, Angelo Antonini, Luigi Bubacco, Rita Barresi, Nicoletta Plotegher, Elisa Greggio, Laura Civiero

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Abstract

Background:

Parkinson’s disease is a progressive neurodegenerative disorder mainly distinguished by sporadic etiology, although a genetic component is also well established. Variants in the LRRK2 gene are associated with both familiar and sporadic disease. We have previously shown that PAK6 and 14-3-3γ protein interact with and regulate the activity of LRRK2.

Objective:

The aim of this study is to quantify PAK6 and 14-3-3γ in plasma as reliable biomarkers for the diagnosis of both sporadic and LRRK2-linked Parkinson’s disease.

Methods:

After an initial quantification of PAK6 and 14-3-3γ expression by means of Western blot in post-mortem human brains, we verified the presence of the two proteins in plasma by using quantitative ELISA tests. We analyzed samples obtained from 39 healthy subjects, 40 patients with sporadic Parkinson’s disease, 50 LRRK2-G2019S non-manifesting carriers and 31 patients with LRRK2-G2019S Parkinson’s disease.

Results:

The amount of PAK6 and 14-3-3γ is significantly different in patients with Parkinson’s disease compared to healthy subjects. Moreover, the amount of PAK6 also varies with the presence of the G2019S mutation in the LRRK2 gene. Although the generalized linear models show a low association between the presence of Parkinson’s disease and PAK6, the kinase could be added in a broader panel of biomarkers for the diagnosis of Parkinson’s disease.

Conclusions:

Changes of PAK6 and 14-3-3γ amount in plasma represent a shared readout for patients affected by sporadic and LRRK2-linked Parkinson’s disease. Overall, they can contribute to the establishment of an extended panel of biomarkers for the diagnosis of Parkinson’s disease.

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PAK6 和 14-3-3γ 作为帕金森病生物标记物的前瞻性作用

摘要背景：帕金森病是一种进行性神经退行性疾病，主要以散发性病因为特征，但遗传因素也已得到证实。LRRK2 基因的变异与熟悉的和散发性疾病均有关联。本研究的目的是定量检测血浆中的 PAK6 和 14-3-3γ，作为诊断散发性帕金森病和 LRRK2 相关帕金森病的可靠生物标志物。方法：在通过 Western 印迹初步定量检测死后人脑中 PAK6 和 14-3-3γ 的表达后，我们通过 ELISA 定量检测验证了这两种蛋白在血浆中的存在。我们分析了来自 39 名健康受试者、40 名散发性帕金森病患者、50 名 LRRK2-G2019S 非显性携带者和 31 名 LRRK2-G2019S 帕金森病患者的样本。此外，PAK6 的含量还随 LRRK2 基因 G2019S 突变的存在而变化。结论：血浆中 PAK6 和 14-3-3γ 含量的变化是散发性帕金森病和 LRRK2 相关帕金森病患者的共同读数。总之，它们有助于建立一个用于诊断帕金森病的扩展生物标记物面板。

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

Journal of Parkinson's disease NEUROSCIENCES-

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.