MAPKAPK2, a potential dynamic network biomarker of α-synuclein prior to its aggregation in PD patients
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 i...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2023-03-01
|
| Series: | npj Parkinson's Disease |
| Online Access: | https://doi.org/10.1038/s41531-023-00479-z |
| _version_ | 1797429488164798464 |
|---|---|
| author | Zhenggang Zhong Jiabao Li Jiayuan Zhong Yilin Huang Jiaqi Hu Piao Zhang Baowen Zhang Yabin Jin Wei Luo Rui Liu Yuhu Zhang Fei Ling |
| author_facet | Zhenggang Zhong Jiabao Li Jiayuan Zhong Yilin Huang Jiaqi Hu Piao Zhang Baowen Zhang Yabin Jin Wei Luo Rui Liu Yuhu Zhang Fei Ling |
| author_sort | Zhenggang Zhong |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T09:13:51Z |
| format | Article |
| id | doaj.art-67d03fc129f144fa88693c52077fcb61 |
| institution | Directory Open Access Journal |
| issn | 2373-8057 |
| language | English |
| last_indexed | 2024-03-09T09:13:51Z |
| publishDate | 2023-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Parkinson's Disease |
| spelling | doaj.art-67d03fc129f144fa88693c52077fcb612023-12-02T07:49:28ZengNature Portfolionpj Parkinson's Disease2373-80572023-03-019111310.1038/s41531-023-00479-zMAPKAPK2, a potential dynamic network biomarker of α-synuclein prior to its aggregation in PD patientsZhenggang Zhong0Jiabao Li1Jiayuan Zhong2Yilin Huang3Jiaqi Hu4Piao Zhang5Baowen Zhang6Yabin Jin7Wei Luo8Rui Liu9Yuhu Zhang10Fei Ling11Guangdong Key Laboratory of Fermentation and Enzyme Engineering, School of Biology and Biological Engineering, South China University of TechnologyGuangdong Key Laboratory of Fermentation and Enzyme Engineering, School of Biology and Biological Engineering, South China University of TechnologySchool of Mathematics, South China University of TechnologyGuangdong Key Laboratory of Fermentation and Enzyme Engineering, School of Biology and Biological Engineering, South China University of TechnologyGuangdong Key Laboratory of Fermentation and Enzyme Engineering, School of Biology and Biological Engineering, South China University of TechnologyDepartment of Neurology, Guangdong Neuroscience Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical SciencesGuangdong Key Laboratory of Fermentation and Enzyme Engineering, School of Biology and Biological Engineering, South China University of TechnologyThe First People’s Hospital of Foshan, Sun Yat-sen UniversityThe First People’s Hospital of Foshan, Sun Yat-sen UniversitySchool of Mathematics, South China University of TechnologyDepartment of Neurology, Guangdong Neuroscience Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical SciencesGuangdong Key Laboratory of Fermentation and Enzyme Engineering, School of Biology and Biological Engineering, South China University of TechnologyAbstract 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.https://doi.org/10.1038/s41531-023-00479-z |
| spellingShingle | Zhenggang Zhong Jiabao Li Jiayuan Zhong Yilin Huang Jiaqi Hu Piao Zhang Baowen Zhang Yabin Jin Wei Luo Rui Liu Yuhu Zhang Fei Ling MAPKAPK2, a potential dynamic network biomarker of α-synuclein prior to its aggregation in PD patients npj Parkinson's Disease |
| title | MAPKAPK2, a potential dynamic network biomarker of α-synuclein prior to its aggregation in PD patients |
| title_full | MAPKAPK2, a potential dynamic network biomarker of α-synuclein prior to its aggregation in PD patients |
| title_fullStr | MAPKAPK2, a potential dynamic network biomarker of α-synuclein prior to its aggregation in PD patients |
| title_full_unstemmed | MAPKAPK2, a potential dynamic network biomarker of α-synuclein prior to its aggregation in PD patients |
| title_short | MAPKAPK2, a potential dynamic network biomarker of α-synuclein prior to its aggregation in PD patients |
| title_sort | mapkapk2 a potential dynamic network biomarker of α synuclein prior to its aggregation in pd patients |
| url | https://doi.org/10.1038/s41531-023-00479-z |
| work_keys_str_mv | AT zhenggangzhong mapkapk2apotentialdynamicnetworkbiomarkerofasynucleinpriortoitsaggregationinpdpatients AT jiabaoli mapkapk2apotentialdynamicnetworkbiomarkerofasynucleinpriortoitsaggregationinpdpatients AT jiayuanzhong mapkapk2apotentialdynamicnetworkbiomarkerofasynucleinpriortoitsaggregationinpdpatients AT yilinhuang mapkapk2apotentialdynamicnetworkbiomarkerofasynucleinpriortoitsaggregationinpdpatients AT jiaqihu mapkapk2apotentialdynamicnetworkbiomarkerofasynucleinpriortoitsaggregationinpdpatients AT piaozhang mapkapk2apotentialdynamicnetworkbiomarkerofasynucleinpriortoitsaggregationinpdpatients AT baowenzhang mapkapk2apotentialdynamicnetworkbiomarkerofasynucleinpriortoitsaggregationinpdpatients AT yabinjin mapkapk2apotentialdynamicnetworkbiomarkerofasynucleinpriortoitsaggregationinpdpatients AT weiluo mapkapk2apotentialdynamicnetworkbiomarkerofasynucleinpriortoitsaggregationinpdpatients AT ruiliu mapkapk2apotentialdynamicnetworkbiomarkerofasynucleinpriortoitsaggregationinpdpatients AT yuhuzhang mapkapk2apotentialdynamicnetworkbiomarkerofasynucleinpriortoitsaggregationinpdpatients AT feiling mapkapk2apotentialdynamicnetworkbiomarkerofasynucleinpriortoitsaggregationinpdpatients |