Inhibition of GSK3 dependent tau phosphorylation by metals.
One of the main pathological characteristics of Alzheimer's disease is the presence in the brain of the patients of an aberrant structure, the paired helical filaments, composed of hyperphosphorylated tau. The level of tau phosphorylation has been correlated with the capacity for tau aggregation. Thus, the mechanism for tau phosphorylation could be important to clarify those pathological features in Alzheimer's disease. Tau protein could be modified by different kinases, being GSK3 the one that could modify more sites of that protein. GSK3 activity could be modulate by the presence of metals like magnesium that can be required for the proper function of the kinase, whereas, metals like manganesum or lithium inhibit the activity of the kinase. Many works have been done to study the inhibition of GSK3 by lithium, a specific inhibitor of that kinase. More recently, it has been indicated that sodium tungstate could also inhibit GSK3 through a different mechanism. In this review, we discuss the effect of these two metals, lithium and tungstate, on GSK3 (or tau I kinase) activity.
Gómez-Ramos
Alberto
A
Centro de Biología Molecular, CSIC/UAM, Facultad de Ciencias, Universidad Autónoma de Madrid, Cantoblanco, E-28049 Madrid, Spain.
Domínguez
Jorge
J
Zafra
Delia
D
Corominola
Helena
H
Gomis
Ramon
R
Guinovart
Joan J
JJ
Avila
Jesús
J
D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D008670:Metals / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D016875:tau Proteins / Q000378:metabolism*
D004791:Enzyme Inhibitors; D008670:Metals; D016875:tau Proteins; D038362:Glycogen Synthase Kinase 3