LINCS Dataset-Based Repositioning of Dutasteride as an Anti-Neuroinflammation Agent

This study explored the repurposing of dutasteride, a 5-α-reductase inhibitor, as an anti-neuroinflammation agent using the LINCS dataset. By comparing the signatures of Lipopolysaccharide (LPS) with compounds in the LINCS database, dutasteride was identified as a promising candidate due to its high blood-brain barrier penetration. In vitro and in vivo experiments demonstrated that dutasteride significantly reduced inflammatory markers IL-6 and TNF-α in LPS-stimulated BV2 cells and decreased IL-6 levels and microglia activation in the brains of LPS-administered mice. Additionally, dutasteride alleviated cognitive impairment in these mice. The study concluded that dutasteride could potentially ameliorate LPS-induced neuroinflammation and cognitive deficits, highlighting the effectiveness of the LINCS dataset-based drug repurposing strategy.