Lithium inhibits Alzheimer's disease‐like tau protein phosphorylation in neurons

FEBS Letters

Avila, Jesús¹  Dı́az-Nido, Javier¹  Moreno, Francisco J.¹  Muñoz-Montaño, Juan Ramón¹ 

[1] Centro de Biologı́a Molecular ‘Severo Ochoa’, Facultad de Ciencias, Universidad Autónoma de Madrid, E-28049 Madrid, Spain

关键词: Alzheimer's disease;    Glycogen synthase kinase-3;    Lithium;    Okadaic acid;    Tau protein;    Rat cerebellar granule neuron;    AD;    Alzheimer's disease;    CDK;    cyclin-dependent kinase;    GSK-3;    glycogen synthase kinase-3;    MAPK;    mitogen-activated protein kinase;    PDPK;    proline-directed protein kinase;    PHF-tau;    tau from paired helical filaments;   

DOI  :  10.1016/S0014-5793(97)00688-1

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

In Alzheimer's disease, tau protein becomes hyperphosporylated, which can contribute to neuronal degeneration. However, the implicated protein kinases are still unknown. Now we report that lithium (an inhibitor of glycogen synthase kinase-3) causes tau dephosphorylation at the sites recognized by antibodies Tau-1 and PHF-1 both in cultured neurons and in vivo in rat brain. This is consistent with a major role for glycogen synthase kinase-3 in modifying proline-directed sites on tau protein within living neurons under physiological conditions. Lithium also blocks the Alzheimer's disease-like proline-directed hyperphosphorylation of tau protein which is observed in neurons treated with a phosphatase inhibitor. These data raise the possibility of using lithium to prevent tau hyperphosphorylation in Alzheimer's disease.

【 授权许可】

Unknown