MAPKAPK2, a potential dynamic network biomarker of α-synuclein prior to its aggregation in PD patients

Zhenggang Zhong; Jiabao Li; Jiayuan Zhong; Yilin Huang; Jiaqi Hu; Piao Zhang; Baowen Zhang; Yabin Jin; Wei Luo; Rui Liu; Yuhu Zhang; Fei Ling

doi:10.1038/s41531-023-00479-z

MAPKAPK2, a potential dynamic network biomarker of α-synuclein prior to its aggregation in PD patients

NPJ Parkinsons Dis. 2023 Mar 16;9(1):41. doi: 10.1038/s41531-023-00479-z.

Authors

Zhenggang Zhong¹, Jiabao Li¹, Jiayuan Zhong², Yilin Huang¹, Jiaqi Hu¹, Piao Zhang³, Baowen Zhang¹, Yabin Jin⁴, Wei Luo⁵, Rui Liu⁶, Yuhu Zhang⁷, Fei Ling⁸

Affiliations

¹ Guangdong Key Laboratory of Fermentation and Enzyme Engineering, School of Biology and Biological Engineering, South China University of Technology, Guangzhou, Guangdong, China.
² School of Mathematics, South China University of Technology, Guangzhou, Guangdong, China.
³ Department of Neurology, Guangdong Neuroscience Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
⁴ The First People's Hospital of Foshan, Sun Yat-sen University, Foshan, China.
⁵ The First People's Hospital of Foshan, Sun Yat-sen University, Foshan, China. luowei_421@163.com.
⁶ School of Mathematics, South China University of Technology, Guangzhou, Guangdong, China. scliurui@scut.edu.cn.
⁷ Department of Neurology, Guangdong Neuroscience Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China. yhzhangsd@126.com.
⁸ Guangdong Key Laboratory of Fermentation and Enzyme Engineering, School of Biology and Biological Engineering, South China University of Technology, Guangzhou, Guangdong, China. fling@scut.edu.cn.

Abstract

One of the important pathological features of Parkinson's disease (PD) is the pathological aggregation of α-synuclein (α-Syn) in the substantia nigra. Preventing the aggregation of α-Syn has become a potential strategy for treating PD. However, the molecular mechanism of α-Syn aggregation is unclear. In this study, using the dynamic network biomarker (DNB) method, we first identified the critical time point when α-Syn undergoes pathological aggregation based on a SH-SY5Y cell model and found that DNB genes encode transcription factors that regulated target genes that were differentially expressed. Interestingly, we found that these DNB genes and their neighbouring genes were significantly enriched in the cellular senescence pathway and thus proposed that the DNB genes HSF1 and MAPKAPK2 regulate the expression of the neighbouring gene SERPINE1. Notably, in Gene Expression Omnibus (GEO) data obtained from substantia nigra, prefrontal cortex and peripheral blood samples, the expression level of MAPKAPK2 was significantly higher in PD patients than in healthy people, suggesting that MAPKAPK2 has potential as an early diagnostic biomarker of diseases related to pathological aggregation of α-Syn, such as PD. These findings provide new insights into the mechanisms underlying the pathological aggregation of α-Syn.