ErbB2pY -1248 as a predictive biomarker for Parkinson's disease based on research with RPPA technology and in vivo verification

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_pY-1248 significantly increased in the MPTP-induced mouse PD model. Our results suggest that ErbB2_pY-1248 is a predictive biomarker for PD.

Conclusions: In this study, we found that ErbB2_pY-1248 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.

Keywords: ErbB2; PD; SH-SY5Y; mouse; reverse phase protein array; zebrafish.