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Pantothenic Acid Protects Neurons After Ischemic Stroke by Targeting ID3 to Restore Action Potential Amplitude
Hongqiao Chen1, Mingli Chen1, Lian Meng1
1Department of Neurology, The First Affiliated Hospital of Guangxi University of Science and Technology, Liuzhou City, Guangxi Zhuang Autonomous Region, China.
None:
Ischemic stroke (IS) remains a devastating condition with limited neuroprotective options. This study investigated the role of the transcription factor inhibitor of DNA binding 3 (ID3) in acute IS through an integrated approach. Combining bioinformatic analysis of Gene Expression Omnibus (GEO) datasets with machine learning (ML) algorithms, we identified ID3 as a consistently downregulated key gene, and its expression level correlated with neurological severity. Functional analysis suggested ID3 modulates neuroinflammation. Furthermore, ID3 and C-type lectin domain family 4 member E (CLEC4E) showed potential as diagnostic biomarkers. Using network pharmacology, pantothenic acid (PA) was predicted as a potential ID3-targeting drug. This was preliminarily tested in an oxygen-glucose deprivation/reperfusion (OGD/R) model, where PA treatment specifically upregulated ID3, ameliorated neuronal electrophysiological dysfunction, and restored action potential amplitude. Our work provides the first integrative evidence suggesting ID3 as a pivotal protective factor in acute IS and nominates PA as a candidate for further development as a neuroprotective agent.
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