Reddy P Hemachandra
Neurogenetics Laboratory, Division of Neuroscience, Oregon National Primate Research Center, Oregon Health & Science University, 505 NW 185th Avenue, Beaverton, OR 97006, USA; Department of Physiology and Pharmacology, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA.
Biochim Biophys Acta. 2013 Dec;1832(12):1913-21. doi: 10.1016/j.bbadis.2013.06.012. Epub 2013 Jun 28.
Glycogen synthase kinase 3 (GSK3) is a serine/threonine protein kinase that is involved in the multiple signaling processes of a cell. Increasing evidence suggests that GSK3β plays a key role in multiple cellular processes in the progression of diabetes, obesity, Alzheimer's disease (AD), Parkinson's disease (PD), inflammatory diseases, schizophrenia, bipolar and several mood disorders, and mitochondrial diseases. Recent research has found that increased GSK3β activity is linked to the pathogenesis of AD through amyloid beta (Aβ), phosphorylated tau and mitochondrial dysfunction. Recent research has also revealed that GSK3β is elevated in AD-affected tissues and is critically involved in dissociating the voltage-dependent anion channel 1 (VDAC1) protein from hexokinases, and causing disrupted glucose metabolism, mitochondrial dysfunction and activating apoptotic cell death. The purpose of this article is to review recent research that is elucidating the role of GSK3β in AD pathogenesis. We discuss the involvement of GSK3β in the phosphorylation of VDAC1 and dissociation of VADC1 with hexokinases in AD neurons.
糖原合酶激酶3（GSK3）是一种丝氨酸/苏氨酸蛋白激酶，参与细胞的多种信号传导过程。越来越多的证据表明，GSK3β在糖尿病、肥胖症、阿尔茨海默病（AD）、帕金森病（PD）、炎症性疾病、精神分裂症、双相情感障碍和几种情绪障碍以及线粒体疾病进展的多种细胞过程中起关键作用。最近的研究发现，GSK3β活性增加通过β淀粉样蛋白（Aβ）、磷酸化tau蛋白和线粒体功能障碍与AD的发病机制相关。最近的研究还表明，GSK3β在受AD影响的组织中升高，并在使电压依赖性阴离子通道1（VDAC1）蛋白与己糖激酶解离、导致葡萄糖代谢紊乱、线粒体功能障碍和激活凋亡性细胞死亡中起关键作用。本文的目的是综述阐明GSK3β在AD发病机制中作用的最新研究。我们讨论了GSK3β在AD神经元中VDAC1磷酸化以及VADC1与己糖激酶解离中的作用。
