M. Hong et al., LITHIUM REDUCES TAU-PHOSPHORYLATION BY INHIBITION OF GLYCOGEN-SYNTHASE KINASE-3, The Journal of biological chemistry, 272(40), 1997, pp. 25326-25332
Lithium is one of the most widely used drugs for treating bipolar (man
ic-depressive) disorder. Despite its efficacy, the molecular mechanism
underlying its action has not been elucidated, One recent study has p
roposed that lithium inhibits glycogen synthase kinase-3 and thereby a
ffects multiple cellular functions, Because glycogen synthase kinase-3
regulates the phosphorylation of tau (microtubule binding protein tha
t forms paired helical filaments in neurons of the Alzheimer's disease
brain), we hypothesized that lithium could affect tau phosphorylation
by inhibiting glycogen synthase kinase-3. Using cultured human NT2N n
eurons, we demonstrate that lithium reduces the phosphorylation of tau
, enhances the binding of tau to microtubules, and promotes microtubul
e assembly through direct and reversible inhibition of glycogen syntha
se kinase-3. These results provide new insights into how Lithium media
tes its effects in the central nervous system, and these findings coul
d be exploited to develop a novel intervention for Alzheimer's disease
.