Glycosylation modulation as a therapeutic strategy for neuroinflammatory disorders: The potential of Tanshinone IIA.

Neuroinflammation is a pivotal pathological process underlying numerous neurological disorders. While the interplay between neuroinflammation and glycosylation is gaining increasing attention, it remains unclear whether modulating glycosylation can effectively inhibit neuroinflammation. To address this, our study employed a combined proteomic and glycoproteomic approach to investigate the role of protein glycosylation in lipopolysaccharide (LPS)-induced neuroinflammation models. There was a significant association between the changes we observed and pathways related to glycation and neuroinflammation. Moreover, during neuroinflammation, protein glycosylation levels exhibit fluctuations. Crucially, we demonstrated that the pan-glycosylation inhibitor NGI-1 effectively suppressed the inflammatory response. We subsequently screened Tanshinone IIA (STS), identifying it as a potent therapeutic candidate for neuroinflammatory disorders. Tanshinone IIA exerts its anti-inflammatory effects partially through the targeted inhibition of Hsp90b1 glycosylation at position 217, thereby attenuating the activation of the NF-κB pathway. Collectively, our findings offer novel insights into the therapeutic potential of targeting glycosylation modifications in neuroinflammation.