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Glycogen synthase kinase-3 (GSK-3) is a pleiotropic serine/threonine protein kinase found in almost all eukaryotes. It is structurally highly conserved and has been identified as a multifaceted enzyme affecting a wide range of biological functions, including gene expression and cellular processes. There are two closely related isoforms of GSK-3; GSK-3α and GSK-3β. The latter appears to play crucial roles in regulating the pathogenesis of diverse diseases, including neurodegenerative disease. The present review focuses on the involvement of this protein in Parkinson’s disease (PD), a common neurodegenerative disorder characterized by the gradually progressive and selective loss of dopaminergic neurons, and by intracellular inclusions known as Lewy bodies (LBs) expressed in surviving neurons of the substantia nigra (SN). GSK-3β is involved in multiple signaling pathways and has several phosphorylation targets. Numerous apoptotic conditions can be facilitated by the GSK-3β signaling pathways. Studies have shown that GSK-3β inhibition protects the dopaminergic neurons from various stress-induced injuries, indicating the involvement of GSK-3β in PD pathogenesis. However, the underlying mechanisms of the protective effect of GSK-3β inhibition on dopaminergic neurons in PD is not completely understood. Multiple pathological events have been recognized to be responsible for the loss of dopaminergic neurons in PD, including mitochondrial dysfunction, oxidative stress, protein aggregation and neuroinflammation. The present review stresses the regulatory roles of GSK-3β in these events and in dopaminergic neuron degeneration, in an attempt to gain an improved understanding of the underlying mechanisms and to provide a potential effective therapeutic target for PD.

Endothelial dysfunction and injury are central events in the pathogenesis of ischemic vascular disorders. Endothelial progenitor cells (EPCs) are mobilized from the bone marrow into the peripheral circulation, where they locate to sites of injured endothelium and are involved in endothelial repair and vascular regeneration. During these processes, EPCs are exposed to oxidative stress, a crucial pathological condition, which occurs during vascular injury and limits the efficacy of EPCs in the repair of injured endothelium. Statins are effective inhibitors of 3‑hydroxy‑3‑methylglutaryl coenzyme A reductase, and are commonly used to manage and prevent ischemic vascular disease by reducing plasma cholesterol levels. In addition to lowering cholesterol, statins have also been reported to exert pleiotropic actions, including anti‑inflammatory and anti‑oxidative activities. The present study aimed to investigate the ability of atorvastatin to protect endothelial colony‑forming cells (ECFCs), a homogeneous subtype of EPCs, from hydrogen peroxide (H2O2)‑induced oxidative damage, and to determine the mechanism underlying this protective action. MTT assay, acridine orange/ethidium bromide staining, reactive oxygen species assay, western blot analysis and tube formation assay were employed. The results demonstrated that H2O2 induced cell death and decreased the tube‑forming ability of the ECFCs, in a concentration‑dependent manner; however, these effects were partially attenuated following administration of atorvastatin. The reversion of the quantitative and qualitative impairment of the H2O2‑treated ECFCs appeared to be mediated by the regulation of annexin A2, as the expression levels of annexin A2 were decreased following treatment with H2O2 and increased following treatment with atorvastatin. These results indicated that annexin A2 may be involved in the H2O2‑induced damage of ECFCs, and in the protective activities of atorvastatin in response to oxidative stress.