Direct and indirect pathways of glycogen synthase kinase 3B inhibition by lithium in culture of neurons

Abstract

In recent years we have given special attention to the possible neuroprotective effects of lithium, especially by the discovery of its regulatory effects on protein pro and anti-apoptotic. The lithium substantially increases the expression of cytoprotective proteins in central nervous system either in rat cortex as in human cells of neural origin. Besides neuroprotective effects, it assists in axon regeneration in the central nervous system of mammals. Lithium downregulates the expression and activity of the enzyme glycogen synthase kinase 3b (GSK3B). The GSK3B plays important roles in brain homeostasis by regulating glycogen synthesis under the influence of insulin cascade beyond the remodeling of the cytoskeleton (synaptic plasticity, neurogenesis and tau protein phosphorylation). The inhibition of this enzyme activity by treatment with lithium may be by direct pathway through phosphorylation of its magnesium sites, or indirectly, via protein kinase phosphorylation B (AKT / PKB), and these effects seem to be one of the targets crucial in therapy with lithium salts. The GSK3B is directly related to the regulation of the levels of phosphorylated tau proteins, which are observed in the neurodegeneration in Alzheimer's disease, as well as cytoskeletal denaturation of nerve cell injury by processes that trigger apoptotic cascades. This study aims to identify the main phosphorylation pathway GSK3B (direct or indirect) for chronic and acute treatment with lithium in neurons and explore through the use of bioinformatics tools associated proteins GSK3B in AD. (AU)