Lithium Inhibits GSK3 β Activity via Two Different Signaling Pathways in Neurons After Spinal Cord Injury.

In this study, we discovered that lithium inhibits GSK3β activity through two different signaling pathways in spinal cord neurons. In the acute phase, lithium inhibited GSK3β activity by stimulating phosphorylation of AKT; in the chronic phase, we first discovered that lithium additionally upregulated the expression of Na+, K+-ATPase α1 (NKA α1), which had an inhibitory effect on GSK3β activity by inducing the expression of glucocorticoid inducible kinase 1 (SGK1). SGK1 is well known as a regulator of the GSK3β/β-catenin signaling pathway. Moreover, the suppressed activity of GSK3β increased the level of β-catenin in the cytoplasm, which gave rise to the translocation of the freely stabilized β-catenin to the nucleus. In addition, the accumulation of β-catenin in the nucleus had the benefits of neuronal survival. Hopefully our findings from this study are beneficial in revealing the neuroprotective mechanism of lithium and in offering novel targets for the development of new SCI therapeutic drugs. PMID: 29404840 [PubMed - as supplied by publisher]
Source: Neurochemical Research - Category: Neuroscience Authors: Tags: Neurochem Res Source Type: research