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

FEBS Lett. 1997 Jul 14;411(2-3):183-8. doi: 10.1016/s0014-5793(97)00688-1.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / metabolism*
  • Animals
  • Blotting, Western
  • Brain / drug effects
  • Brain / metabolism*
  • Calcium-Calmodulin-Dependent Protein Kinases / antagonists & inhibitors
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism
  • Cells, Cultured
  • Cyclin-Dependent Kinases / antagonists & inhibitors
  • Enzyme Inhibitors / pharmacology
  • Flavonoids / pharmacology
  • Glycogen Synthase Kinase 3
  • Glycogen Synthase Kinases
  • Humans
  • Kinetin
  • Lithium / pharmacology*
  • Neurons / drug effects
  • Neurons / metabolism*
  • Okadaic Acid / pharmacology
  • Phosphorylation / drug effects
  • Proline / metabolism
  • Purines / pharmacology
  • Rats
  • tau Proteins / immunology
  • tau Proteins / metabolism*

Substances

  • Enzyme Inhibitors
  • Flavonoids
  • Purines
  • tau Proteins
  • Okadaic Acid
  • olomoucine
  • Proline
  • Lithium
  • Glycogen Synthase Kinases
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Cyclin-Dependent Kinases
  • Glycogen Synthase Kinase 3
  • Kinetin
  • 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one