• Discovering molecular drivers...

*Result*: Discovering molecular drivers of human epileptogenesis through integrative multi-omics profiling.

Title:
Discovering molecular drivers of human epileptogenesis through integrative multi-omics profiling.
Authors:
Zhou N; Cell Biology Research Laboratory, Public Research Platform of Basic Medical College, School of Basic Medicine, Hebei Medical University, Shijiazhuang, Hebei 050017, China; The Key Laboratory of Neural and Vascular Biology, Ministry of Education, The Key Laboratory of New Drug Pharmacology and Toxicology, Hebei Medical University, Shijiazhuang, Hebei 050017, China; Collaborative Innovation Center of Hebei Province for Mechanism, Diagnosis and Treatment of Neuropsychiatric Diseases, Shijiazhuang, Hebei, China. Electronic address: njingzhou@hebmu.edu.cn., Yan Y; Cell Biology Research Laboratory, Public Research Platform of Basic Medical College, School of Basic Medicine, Hebei Medical University, Shijiazhuang, Hebei 050017, China. Electronic address: 18100832@hebmu.edu.cn., Zhang D; Department of Pharmacology, School of Basic Medicine, Hebei Medical University, Shijiazhuang, Hebei 050017, China; Department of Neurosurgery of Second Hospital, Hebei Medical University, Shijiazhuang, Hebei 050017, China. Electronic address: zhangdi_92@hebmu.edu.cn., Di Y; Department of Pharmacology, School of Basic Medicine, Hebei Medical University, Shijiazhuang, Hebei 050017, China. Electronic address: 20201042@stu.hedmu.edu.cn., Gang W; Department of Pharmacology, School of Basic Medicine, Hebei Medical University, Shijiazhuang, Hebei 050017, China., Yuan Y; Department of Pharmacology, School of Basic Medicine, Hebei Medical University, Shijiazhuang, Hebei 050017, China; Collaborative Innovation Center of Hebei Province for Mechanism, Diagnosis and Treatment of Neuropsychiatric Diseases, Shijiazhuang, Hebei, China., Zhang J; Department of Neurosurgery of Second Hospital, Hebei Medical University, Shijiazhuang, Hebei 050017, China. Electronic address: 28805565@hebmu.edu.cn., Zhang H; Department of Pharmacology, School of Basic Medicine, Hebei Medical University, Shijiazhuang, Hebei 050017, China; The Key Laboratory of Neural and Vascular Biology, Ministry of Education, The Key Laboratory of New Drug Pharmacology and Toxicology, Hebei Medical University, Shijiazhuang, Hebei 050017, China; Department of Biopharmaceutics, Hebei Medical University, Shijiazhuang, Hebei 050017, China. Electronic address: zhanghr@hebmu.edu.cn., Qu K; Cell Biology Research Laboratory, Public Research Platform of Basic Medical College, School of Basic Medicine, Hebei Medical University, Shijiazhuang, Hebei 050017, China. Electronic address: 22033070023@stu.hebmu.edu.cn., Zhao W; Department of Pharmacology, School of Basic Medicine, Hebei Medical University, Shijiazhuang, Hebei 050017, China. Electronic address: 19101665@hebmu.edu.cn., Dai J; Shanghai BioProfile Technology CO., LTD, Shanghai 200000, China. Electronic address: jie.dai@bioprofile.cn., Du X; Department of Pharmacology, School of Basic Medicine, Hebei Medical University, Shijiazhuang, Hebei 050017, China; The Key Laboratory of Neural and Vascular Biology, Ministry of Education, The Key Laboratory of New Drug Pharmacology and Toxicology, Hebei Medical University, Shijiazhuang, Hebei 050017, China; Collaborative Innovation Center of Hebei Province for Mechanism, Diagnosis and Treatment of Neuropsychiatric Diseases, Shijiazhuang, Hebei, China. Electronic address: duxiaona@hebmu.edu.cn., Li W; Department of Neurosurgery of Second Hospital, Hebei Medical University, Shijiazhuang, Hebei 050017, China; Collaborative Innovation Center of Hebei Province for Mechanism, Diagnosis and Treatment of Neuropsychiatric Diseases, Shijiazhuang, Hebei, China. Electronic address: 27104413@hebmu.edu.cn., Zhang H; Department of Pharmacology, School of Basic Medicine, Hebei Medical University, Shijiazhuang, Hebei 050017, China; The Key Laboratory of Neural and Vascular Biology, Ministry of Education, The Key Laboratory of New Drug Pharmacology and Toxicology, Hebei Medical University, Shijiazhuang, Hebei 050017, China; Department of Psychiatry, The First Hospital of Hebei Medical University, Mental Health Institute of Hebei Medical University, Shijiazhuang, Hebei, China; Collaborative Innovation Center of Hebei Province for Mechanism, Diagnosis and Treatment of Neuropsychiatric Diseases, Shijiazhuang, Hebei, China. Electronic address: zhanghl@hebmu.edu.cn.
Source:
Neurobiology of disease [Neurobiol Dis] 2025 Dec; Vol. 217, pp. 107165. Date of Electronic Publication: 2025 Oct 28.
Publication Type:
Journal Article
Language:
English
Journal Info:
Publisher: Academic Press Country of Publication: United States NLM ID: 9500169 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1095-953X (Electronic) Linking ISSN: 09699961 NLM ISO Abbreviation: Neurobiol Dis Subsets: MEDLINE
Imprint Name(s):
Publication: San Diego, CA : Academic Press
Original Publication: Oxford : Blackwell Science, c1994-
MeSH Terms:
Epilepsy*/genetics , Epilepsy*/metabolism , Proteomics*/methods , Brain*/metabolism, Drug Resistant Epilepsy/metabolism ; Drug Resistant Epilepsy/genetics ; Biomarkers/metabolism ; Humans ; Female ; Male ; Adult ; Gene Expression Profiling ; Multiomics
Contributed Indexing:
Keywords: Epilepsy; Epileptogenesis; Epileptogenic zone; Multi-omics; Seizure onset zone
Substance Nomenclature:
0 (Biomarkers)
Entry Date(s):
Date Created: 20251030 Date Completed: 20251206 Latest Revision: 20251210
Update Code:
20260130
DOI:
10.1016/j.nbd.2025.107165
PMID:
41167490
Database:
MEDLINE

*Further Information*

*Epilepsy is a neurological disorder affecting millions worldwide, with drug-resistant epilepsy posing a major treatment challenge. Despite extensive research, the molecular mechanisms underlying epileptogenesis remain incompletely understood. To identify novel biomarkers and therapeutic targets, an integrated multi-omics approach was employed, analyzing Data-Independent Acquisition (DIA) and Parallel Reaction Monitoring (PRM) proteomics, bulk RNA-seq, and single-nucleus RNA-seq (snRNA-seq) data. Human brain tissues from epilepsy surgeries were divided into three groups: the seizure onset zone (Core, C), marginal excision tissue (Border, B), and non-epileptic controls (N). Differentially expressed proteins (DEPs) and genes (DEGs) were identified across groups. Key molecules, OXR1, GLRX, CCK, and PLCB1 emerged as potential drivers of epilepsy progression, offering insights into epileptic discharge mechanisms and disease development. These findings highlight promising targets for future therapies. CLINICAL PERSPECTIVES: Epilepsy, particularly drug-resistant forms, poses significant treatment challenges due to limited understanding of its molecular mechanisms. This study was undertaken to identify key biomarkers and therapeutic targets through integrative multi-omics profiling of human epileptic tissues, addressing gaps left by animal models and inconsistent prior research. Analyzing surgical samples from the seizure onset zone (Core), adjacent border tissue (Border), and non-epileptic controls, the study revealed consistent alterations in proteins (e.g., OXR1, GLRX, CCK, PLCB1) and genes across these regions. These molecules are implicated in oxidative stress, synaptic signaling, and neuronal excitability, offering insights into epileptogenesis. The findings highlight potential targets for novel therapies, particularly for drug-resistant epilepsy, and underscore the importance of glial and neuronal interactions in disease progression. By bridging proteomic and transcriptomic data, this research advances precision medicine approaches, paving the way for improved diagnostics and targeted treatments to mitigate seizure burden and enhance patient outcomes.
(Copyright © 2024. Published by Elsevier Inc.)*

*Declaration of competing interest The authors declare that they have no conflict of interest.*