海马硬化
神经科学
癫痫
神经炎症
药物重新定位
药物发现
疾病
药物开发
生物
神经传递
转录组
少突胶质细胞
癫痫发生
计算生物学
颞叶
医学
药品
生物信息学
基因
药理学
受体
基因表达
遗传学
中枢神经系统
病理
髓鞘
作者
Liesbeth François,Alessia Romagnolo,Mark J. Luinenburg,Jasper J. Anink,Patrice Godard,Marek Rajman,Jonathan van Eyll,Angelika Mühlebner,Andrew Skelton,James D. Mills,Stefanie Dedeurwaerdere,Eleonora Aronica
标识
DOI:10.1038/s41467-024-46592-2
摘要
Abstract Epilepsy is a chronic and heterogenous disease characterized by recurrent unprovoked seizures, that are commonly resistant to antiseizure medications. This study applies a transcriptome network-based approach across epilepsies aiming to improve understanding of molecular disease pathobiology, recognize affected biological mechanisms and apply causal reasoning to identify therapeutic hypotheses. This study included the most common drug-resistant epilepsies (DREs), such as temporal lobe epilepsy with hippocampal sclerosis (TLE-HS), and mTOR pathway-related malformations of cortical development (mTORopathies). This systematic comparison characterized the global molecular signature of epilepsies, elucidating the key underlying mechanisms of disease pathology including neurotransmission and synaptic plasticity, brain extracellular matrix and energy metabolism. In addition, specific dysregulations in neuroinflammation and oligodendrocyte function were observed in TLE-HS and mTORopathies, respectively. The aforementioned mechanisms are proposed as molecular hallmarks of DRE with the identified upstream regulators offering opportunities for drug-target discovery and development.
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