1Department of Biotechnology, Vels Institute of Science, Technology and Advanced Studies (VISTAS), Pallavaram, Chennai-600117, Tamil Nadu, India.
*Corresponding author: vardhana88@ymail.com
Background: Levetiracetam (LEV), an antiepileptic drug of the second generation, has shown neuroprotective activity in addition to antiepileptic activity, in particular against oxidative stress-induced neuronal damage. The researchers tested the effects of finding out whether LEV can reduce the neurotoxicity effects of lead acetate in human SH-SY5Y neuroblastoma cell line via a whole-transcriptome NGS.
Results: There was an interference of gene networks concerning oxidative stress management, apoptosis, lipid metabolism, and synaptic signalling with lead acetate exposure. LEV pretreatment significantly counteracted these changes and stimulated genes involved in antioxidant protection, neuronal survival, extracellular component organization, and nicotinic plasticity and inhibited the pro-apoptotic pathway and the genes related to cholesterol biosynthesis. KEGG pathway and functional enrichment analysis showed that TGF-beta, PI3K-Akt and metal ion detoxification pathways were notably covered, and excitation-inhibition balance restoration of gene expression was restored. PPI mapping identified major hub genes linked to survival signalling and extracellular matrix stability, including as TIMP1, IGFBP5, ID1/2/3, and DCN.
Conclusion: These data imply that LEV has transcriptional neuroprotection that enables neuroprotection due to the promotion of the detoxication processes, maintenance of synaptic integrity, and inhibition of the metal and metabolic stress responses, which underlines its repositioning as a possible treatment of neurodegenerative disorders linked to environmental neurotoxins.
Keywords: Levetiracetam, neuroprotection, lead acetate, oxidative stress, SH-SY5Y cells, transcriptomics, gene expression, Alzheimer's disease.
How to cite this article: Karthikeyan TA, Vardhana J. Transcriptomic Insights into Levetiracetam's Neuroprotective Mechanisms Against Lead-Induced Toxicity in SH-SY5Y cells. Int J Drug Deliv Technol. 2026;16(13s): 212-229. DOI: 10.25258/ijddt.16.13s.23
Source of support: Nil.
Conflict of interest: None