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基于 RPPA 技术的研究和体内验证，ErbB2 作为帕金森病的预测性生物标志物。

ErbB2 as a predictive biomarker for Parkinson's disease based on research with RPPA technology and in vivo verification.

机构信息

Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), Ji'nan, China.

Engineering Research Center of Zebrafish Models for Human Diseases and Drug Screening of Shandong Province, Ji'nan, China.

出版信息

CNS Neurosci Ther. 2024 Feb;30(2):e14407. doi: 10.1111/cns.14407. Epub 2023 Aug 11.

DOI:10.1111/cns.14407
PMID:37564024
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10848095/
Abstract

AIMS

This study aims to reveal a promising biomarker for Parkinson's disease (PD) based on research with reverse phase protein array (RPPA) technology for the first time and in vivo verification, which gains time for early intervention in PD, thus increasing the effectiveness of treatment and reducing disease morbidity.

METHODS AND RESULTS

We employed RPPA technology which can assess both total and post-translationally modified proteins to identify biomarker candidates of PD in a cellular PD model. As a result, the phosphorylation (pY-1248) of the epidermal growth factor receptor (EGFR) ErbB2 is a promising biomarker candidate for PD. In addition, lapatinib, an ErbB2 tyrosine kinase inhibitor, was used to verify this PD biomarker candidate in vivo. We found that lapatinib-attenuated dopaminergic neuron loss and PD-like behavior in the zebrafish PD model. Accordingly, the expression of ErbB2 significantly increased in the MPTP-induced mouse PD model. Our results suggest that ErbB2 is a predictive biomarker for PD.

CONCLUSIONS

In this study, we found that ErbB2 is a predictive biomarker of PD by using RPPA technology and in vivo verification. It offers a new perspective on PD diagnosing and treatment, which will be essential in identifying individuals at risk of PD. In addition, this study provides new ideas for digging into biomarkers of other neurodegenerative diseases.

摘要

目的

本研究旨在利用反向蛋白质阵列（RPPA）技术首次进行体内验证，寻找帕金森病（PD）的潜在生物标志物，为 PD 的早期干预争取时间，从而提高治疗效果，降低疾病发病率。

方法和结果

我们采用 RPPA 技术，可评估总蛋白和翻译后修饰蛋白，以鉴定 PD 细胞模型中的生物标志物候选物。结果表明，表皮生长因子受体（EGFR）ErbB2 的磷酸化（pY-1248）是 PD 的一个有前途的生物标志物候选物。此外，我们使用 ErbB2 酪氨酸激酶抑制剂拉帕替尼在体内验证了这个 PD 生物标志物候选物。我们发现拉帕替尼可减轻斑马鱼 PD 模型中多巴胺能神经元的丢失和 PD 样行为。因此，在 MPTP 诱导的小鼠 PD 模型中，ErbB2 的表达显著增加。我们的结果表明，ErbB2 是 PD 的预测生物标志物。

结论

本研究通过 RPPA 技术和体内验证发现 ErbB2 是 PD 的预测生物标志物。这为 PD 的诊断和治疗提供了新的视角，对于识别 PD 高危人群至关重要。此外，本研究为挖掘其他神经退行性疾病的生物标志物提供了新的思路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7e04/10848095/9ed2ee0ad3e2/CNS-30-e14407-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7e04/10848095/2531265907cd/CNS-30-e14407-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7e04/10848095/37cb98d1c0cd/CNS-30-e14407-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7e04/10848095/e54a5731ff97/CNS-30-e14407-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7e04/10848095/038eea802862/CNS-30-e14407-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7e04/10848095/bf0caf5a8645/CNS-30-e14407-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7e04/10848095/2e53b8be65b0/CNS-30-e14407-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7e04/10848095/9ed2ee0ad3e2/CNS-30-e14407-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7e04/10848095/2531265907cd/CNS-30-e14407-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7e04/10848095/37cb98d1c0cd/CNS-30-e14407-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7e04/10848095/e54a5731ff97/CNS-30-e14407-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7e04/10848095/038eea802862/CNS-30-e14407-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7e04/10848095/bf0caf5a8645/CNS-30-e14407-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7e04/10848095/2e53b8be65b0/CNS-30-e14407-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7e04/10848095/9ed2ee0ad3e2/CNS-30-e14407-g003.jpg

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