GSK3 and Alzheimer’s disease

     Glycogen synthase kinase 3 (GSK-3), as a serine/threonine protein kinase, can contribute to phosphorylating and thus inactivating glycogen synthase, and also been involved in the control of cellular response to damaged DNA.
     There are two isozymes that are identified as GSK3α and GSK3β. They share the 84% sequence identity, while not have the identical function as are reported by in vitro, cellular,and in vivo data [1]. Complete lack of GSK3β is embryonically lethal in mice, suggesting that GSK3α cannot compensate for the function of GSK3β[2].  however, GSK3α defect will not cause significant adverse effects on viability or health, except male sterility[3].
     Both GSK3 isozymes have been considered to differentially involve in regulation of neuronal survival, and both contribute to axon formation in different mechanisms. Recent studies reported that various structural and physiological functions of the GSK3 isozymes can be observed in peripheral organs and in brain[4]. Alzheimer's dementia is a chronic, progressive disorder beginning with mild symptoms that are hard to recognize, and amyloid peptides and tau abnormality are the main cause of AD. Amyloid peptides can indirectly affect the activity of phosphatases and even more so of kinases,in particular GSK3β. GSK3β is also reported to be a most efficient Tau kinase, necessary but not sufficient to drive tau to aggregate into fibrils[5].
     In summary, GSK3 play an important role in brain function as well as brain dysfunction in AD. In the following articles, the details will be continued to explore.

References
[1]. J. Neurochem. 2010; 115, 974–983.
[2]. Nature 2000; 406, 86–90.
[3]. Mol. Brain 2010; 2, 35.
[4]. J. Neurochem. 2010; 115, 974–983.
[5]. Frontiers in Molecular Neuroscience. 2011; doi:10.3389/fnmol.2011.00017.