Thiamet G

Description	Thiamet G is a potent, selective, and blood brain barrier permeable inhibitor of O-GlcNAcase that demonstrates a Ki value of 21 nM. This compound has been shown to increase cellular O-GlcNAc-modified protein levels (EC50 = 30 nM) and block phosphorylation of tau protein both in cultured PC-12 cells and in rats. Research has shown that hyperphosphorylation of the tau protein can lead to its aggregation and subsequent formation of neurofibrillary tangles, a hallmark of Alzheimer’s disease and other tauopathic, neurodegenerative disorders. Tau is also dynamically modified by the addition and cleavage of O-linked β-N-acetylglucosamine (O-GlcNAc) moieties, which is mediated in part by O-GlcNAcase. Levels of O-GlcNAcylated proteins from Alzheimer’s disease brain extracts are decreased as compared to that in controls, suggesting that impaired brain glucose metabolism may contribute to pathogenesis.
Pathways	Others Pathway
Targets	Autophagy

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