| 9271202 |
Munoz-Montano JR, Moreno FJ, Avila J, Diaz-Nido J: Lithium inhibits Alzheimer's disease-like tau protein phosphorylation in neurons. FEBS Lett. 1997 Jul 14;411(2-3):183-8.
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. |
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