Aghdam Saeed Yadranji, Barger Steven W
School of Biology, University of Tehran, Tehran 14155-6455, Iran.
Curr Alzheimer Res. 2007 Feb;4(1):21-31. doi: 10.2174/156720507779939832.
For over fifty years lithium has been a fundamental component of therapy for patients with bipolar disorders. Lithium has been considered recently for its potential to alleviate neuronal loss and other neurodegeneration processes. For instance, lithium reduces the severity of some behavioral complications of Alzheimer's disease (AD). And there are growing indications that lithium may be of benefit to the underlying pathology of AD, as well as an array of other common CNS disorders, including stroke, Parkinson's disease, and Huntington's disease. Despite these demonstrated and prospective therapeutic benefits, lithium's mechanism of action remains elusive, and opinions differ regarding the most relevant molecular targets. Lithium inhibits several enzymes; significant among these are inositol monophosphatase (IMPase), glycogen synthase kinase-3 (GSK-3), and the proteasome. Most recent publications discussing the medical application of lithium have converged on GSK-3, so this article reviews data and discussions regarding the roles and interactions of GSK-3 with other proteins and its proposed role in the pathogenesis of Alzheimer's disease.
五十多年来，锂一直是双相情感障碍患者治疗的基本组成部分。最近，锂因其减轻神经元损失和其他神经退行性变过程的潜力而受到关注。例如，锂可减轻阿尔茨海默病（AD）某些行为并发症的严重程度。越来越多的迹象表明，锂可能对AD的潜在病理以及一系列其他常见的中枢神经系统疾病有益，包括中风、帕金森病和亨廷顿病。尽管有这些已证实的和潜在的治疗益处，但锂的作用机制仍然难以捉摸，关于最相关的分子靶点也存在不同观点。锂抑制多种酶；其中重要的有肌醇单磷酸酶（IMPase）、糖原合酶激酶-3（GSK-3）和蛋白酶体。最近讨论锂医学应用的出版物大多聚焦于GSK-3，因此本文回顾了有关GSK-3与其他蛋白质的作用和相互作用及其在阿尔茨海默病发病机制中假定作用的数据和讨论。
