Yen, Shu‐Hui

AbstractBackgroundPathological hallmarks of Alzheimer's disease (AD) are senile plaques (SPs) and neurofibrillary tangles (NFTs), which are formed from highly phosphorylated tau. Lithium chloride (LiCl) has been shown to inhibit phosphorylated tau by inhibiting glycogen synthase kinase‐3β (GSK‐3β). In addition, autophagy lysosome system (Hamano et al., Eur J Neurosci 27; 1119, 2008) and proteasome (J Neurochem 2000) are known to play an important role as tau degradation pathways. We investigated the decrease of phosphorylated tau by LiCl by using cell culture model expressing wild‐type tau via TetOff induction system.MethodsTen to 50mM of LiCl treatment (24 hours) was performed to neuroblastoma cells (M1C) expressing wild‐type tau protein (4R0N) via TetOff induction. Total and phosphorylated tau (PHF‐1) levels and autophagy activation were examined by Western blot (WB) analysis.ResultsReduction of total tau (Tau5) and phosphorylated tau (PHF‐1, and CP13) with LiCl treatment was detected by WB analysis. C‐terminal truncated tau species detected by TauC3 was decreased by LiCl, too. In addition, increase of LC3Ⅱ/I, and decrease of P62 suggesting autophagy activation was observed. Major Tau kinase GSK3β was inactivated by LiCl.ConclusionsThese results imply that LiCl may decrease the phosphorylated tau through suppression of tau phosphokinase and activation of autophagy.