Gómez-Ramos Alberto, Domínguez Jorge, Zafra Delia, Corominola Helena, Gomis Ramon, Guinovart Joan J, Avila Jesús
Centro de Biología Molecular, CSIC/UAM, Facultad de Ciencias, Universidad Autónoma de Madrid, Cantoblanco, E-28049 Madrid, Spain.
Curr Alzheimer Res. 2006 Apr;3(2):123-7. doi: 10.2174/156720506776383059.
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.
阿尔茨海默病的主要病理特征之一是患者大脑中存在一种异常结构，即由高度磷酸化的tau组成的双螺旋丝。tau的磷酸化水平与tau聚集能力相关。因此，tau磷酸化机制对于阐明阿尔茨海默病的那些病理特征可能很重要。tau蛋白可被不同的激酶修饰，其中糖原合酶激酶3（GSK3）是能够修饰该蛋白更多位点的激酶。GSK3的活性可受到镁等金属的调节，而镁是该激酶正常功能所必需的，而锰或锂等金属则会抑制该激酶的活性。已经开展了许多工作来研究锂（该激酶的特异性抑制剂）对GSK3的抑制作用。最近，有研究表明钨酸钠也可通过不同机制抑制GSK3。在本综述中，我们讨论锂和钨酸盐这两种金属对GSK3（或tau I激酶）活性的影响。
