自噬
陶氏病
神经退行性变
海藻糖
细胞生物学
内生
τ蛋白
化学
程序性细胞死亡
磷酸化
生物
生物化学
阿尔茨海默病
细胞凋亡
医学
内科学
疾病
作者
Ulrike Krüger,Yipeng Wang,Satish Kumar,Eva‐Maria Mandelkow
标识
DOI:10.1016/j.neurobiolaging.2011.11.009
摘要
Modulating the tau level may represent a therapeutic target for Alzheimer's disease (AD), as accumulating evidence shows that Abeta-induced neurodegeneration is mediated by tau. It is therefore important to understand the expression and degradation of tau in neurons. Recently we showed that overexpressed mutant tau and tau aggregates are degraded via the autophagic pathway in an N2a cell model. Here we investigated whether autophagy is involved in the degradation of endogenous tau in cultured primary neurons. We activated this pathway in primary neurons with trehalose, an enhancer of autophagy. This resulted in the reduction of endogenous tau protein. Tau phosphorylation at several sites elevated in AD pathology had little influence on its degradation by autophagy. Furthermore, by using a neuronal cell model of tauopathy, we showed that activation of autophagy suppresses tau aggregation and eliminates cytotoxicity. Notably, apart from activating autophagy, trehalose also inhibits tau aggregation directly. Thus, trehalose may be a good candidate for developing therapeutic strategies for AD and other tauopathies.
科研通智能强力驱动
Strongly Powered by AbleSci AI