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.

Details

Title
MAPKAPK2, a potential dynamic network biomarker of α-synuclein prior to its aggregation in PD patients
Author
Zhong, Zhenggang 1 ; Li, Jiabao 1 ; Zhong, Jiayuan 2 ; Huang, Yilin 1 ; Hu, Jiaqi 1 ; Zhang, Piao 3 ; Zhang, Baowen 1 ; Jin, Yabin 4 ; Luo, Wei 4 ; Liu, Rui 2   VIAFID ORCID Logo  ; Zhang, Yuhu 3   VIAFID ORCID Logo  ; Ling, Fei 1 

 Guangdong Key Laboratory of Fermentation and Enzyme Engineering, School of Biology and Biological Engineering, South China University of Technology, Guangzhou, China (GRID:grid.79703.3a) (ISNI:0000 0004 1764 3838) 
 South China University of Technology, School of Mathematics, Guangzhou, China (GRID:grid.79703.3a) (ISNI:0000 0004 1764 3838) 
 Guangdong Neuroscience Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Department of Neurology, Guangzhou, China (GRID:grid.79703.3a) 
 Sun Yat-sen University, The First People’s Hospital of Foshan, Foshan, China (GRID:grid.12981.33) (ISNI:0000 0001 2360 039X) 
Pages
41
Publication year
2023
Publication date
2023
Publisher
Nature Publishing Group
e-ISSN
23738057
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2787389739
Copyright
© The Author(s) 2023. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.