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The Interplay Between Epilepsy and Parkinson’s Disease: Gene Expression Profiling and Functional Analysis

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Abstract

The results of many epidemiological studies suggest a bidirectional causality may exist between epilepsy and Parkinson’s disease (PD). However, the underlying molecular landscape linking these two diseases remains largely unknown. This study aimed to explore this possible bidirectional causality by identifying differentially expressed genes (DEGs) in each disease as well as their intersection based on two respective disease-related datasets. We performed enrichment analyses and explored immune cell infiltration based on an intersection of the DEGs. Identifying a protein–protein interaction (PPI) network between epilepsy and PD, and this network was visualised using Cytoscape software to screen key modules and hub genes. Finally, exploring the diagnostic values of the identified hub genes. NetworkAnalyst 3.0 and Cytoscape software were also used to construct and visualise the transcription factor–micro-RNA regulatory and co-regulatory networks, the gene–microRNA interaction network, as well as gene-disease association. Based on the enrichment results, the intersection of the DEGs mainly revealed enrichment in immunity-, phosphorylation-, metabolism-, and inflammation-related pathways. The boxplots revealed similar trends in infiltration of many immune cells in epilepsy and Parkinson’s disease, with greater infiltration in patients than in controls. A complex PPI network comprising 186 nodes and 512 edges were constructed. According to node connection degree, top 15 hub genes were considered the kernel targets of epilepsy and PD. The area under curve values of hub gene expression profiles confirmed their excellent diagnostic values. This study is the first to analyse the molecular landscape underlying the epidemiological link between epilepsy and Parkinson’s disease. The two diseases are closely linked through immunity-, inflammation-, and metabolism-related pathways. This information was of great help in understanding the pathogenesis, diagnosis, and treatment of the diseases. The present results may provide guidance for further in-depth analysis about molecular mechanisms of epilepsy and PD and novel potential targets.

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Data Availability

The datasets generated and/or analysed during the current study are available in the GEO database (https://www.ncbi.nlm.nih.gov/geo/).

Abbreviations

AMPH:

Amphiphysin

ATP:

Adenosine triphosphate

AUC:

Area under the curve

AXIN1:

Axin 1

BP:

Biological process

CC:

Cellular Component

ChEA:

Chromatin Immunoprecipitation Enrichment Analysis

CREM:

Cyclic adenosine monophosphate responsive element modulator

DEGs:

Differentially expressed genes

DNM1:

Dynamin 1

EGR1:

Early growth response factor 1

FLI1:

Fli-1 proto-oncogene

GABA:

γ-Aminobutryic acid

GO:

Gene ontology

HIF-1:

Hypoxia-inducible factor 1

HN4FA:

Hepatocyte nuclear factor 4 alpha

IL-6:

Interleukin 6

IRF7:

Interferon regulatory factor 7

KEGG:

Kyoto Encyclopedia of Genes and Genomes

MCC:

Maximal clique centrality

MCM4:

Minimicrosome maintenance complex component 4

MCODE:

Molecular Complex Detection

miRNA:

Micro-ribonucleic acid

MF:

Molecular Function

MNC:

Maximum neighbourhood component

MRT4:

MRT4 homolog, ribosome maturation factor

MYC:

MYC proto-oncogene

NF:

Nuclear factor

PD:

Parkinson’s disease

PLCG2:

Phospholipase C gamma 2

PPI:

Protein–protein interaction

PPP2R1A:

Protein phosphatase 2 scaffold subunit A alpha

PTPN6:

Protein tyrosine phosphatase non-receptor type 6

ROC:

Receiver operating characteristic

RELA:

RELA proto-oncogene

ROC:

Receiver operating characteristic

RPS3:

Ribosomal protein S3

RPS6:

Ribosomal protein S6

SMARCA4:

Transcription activator BRG1

SMURF2:

SMAD-specific E3 ubiquitin protein ligase 2

SN:

Substantia nigra

SOFT:

Simple Omnibus Format in Text

SPI1:

Spi-1 proton-oncogene

ssGSEA:

Single-sample gene set enrichment analysis

STRING:

Search Tool for the Retrieval of Interacting Genes

SYNJ1:

Synaptojanin 1

TAL1:

T cell acute lymphoblastic lymphoma 1

TF:

Transcription factor

TLE:

Temporal lobe epilepsy

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Acknowledgements

We are thankful to Prof. Guoguang Zhao, for critically editing the current manuscript.

Funding

This research was supported by the National Natural Science Foundation of China (82030037), the STI2030-Major Projects (2021ZD0201801), the Beijing Municipal Science & Technology Commission (Z221100007422016, Z221100002722007), the Translational and Application Project of Brain-inspired and Network Neuroscience on Brain Disorders, Beijing Municipal Health Commission (11000023T000002036286), the Beijing Municipal Health Commission (2022-1-8011, 2022-2-2011), the Ministry of Science and Technology of China (2022YFC2405302), the Beijing Natural Science Foundation (L222107), the National Natural Science Foundation of China (82201605).

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Authors and Affiliations

  1. Department of Neurosurgery, Xuan Wu Hospital of the Capital Medical University, Beijing, 100053, China

    Xiaolong Wu, Kailiang Wang, Jingjing Wang, Penghu Wei, Huaqiang Zhang, Yanfeng Yang, Yinchun Huang, Yihe Wang, Wenli Shi, Yongzhi Shan & Guoguang Zhao

  2. International Neuroscience Institute (China-INI), Beijing, China

    Xiaolong Wu, Kailiang Wang, Jingjing Wang, Penghu Wei, Huaqiang Zhang, Yanfeng Yang, Yinchun Huang, Yihe Wang, Wenli Shi, Yongzhi Shan & Guoguang Zhao

  3. Clinical Research Center for Epilepsy Capital Medical University, Beijing, 100053, China

    Xiaolong Wu, Kailiang Wang, Jingjing Wang, Penghu Wei, Huaqiang Zhang, Yanfeng Yang, Yinchun Huang, Yihe Wang, Wenli Shi, Yongzhi Shan & Guoguang Zhao

  4. Beijing Municipal Geriatric Medical Research Center, Beijing, 100053, China

    Guoguang Zhao

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Contributions

Conceptualisation: XW; Data Collection, XW, YH, WS; Methodology, XW, KW, JW, PW, HZ, YY, YW; Writing, XW; Review and editing: GZ, YS, PW. All authors have read and agreed to the published version of the manuscript.

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Correspondence to Guoguang Zhao.

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Wu, X., Wang, K., Wang, J. et al. The Interplay Between Epilepsy and Parkinson’s Disease: Gene Expression Profiling and Functional Analysis. Mol Biotechnol (2024). https://doi.org/10.1007/s12033-024-01103-y

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