Association of glycogen synthase kinase-3β with Parkinson’s disease (Review)
| Autor: | Guang‑Ren Li, Zhi-Qiang Liu, Wei Chen, Da‑Wei Li, Min Yao |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Fetal Proteins
Cancer Research Parkinson's disease Substantia nigra Apoptosis macromolecular substances Biology Biochemistry glycogen synthase kinase-3β chemistry.chemical_compound Glycogen Synthase Kinase 3 GSK-3 Genetics medicine Animals Humans Protein kinase A Glycogen synthase Molecular Biology GSK3B Alpha-synuclein Inflammation Electron Transport Complex I Glycogen Synthase Kinase 3 beta Dopaminergic regulation Parkinson Disease Articles medicine.disease Cell biology Mitochondria Oncology chemistry Gene Expression Regulation biology.protein Parkinson’s disease alpha-Synuclein Molecular Medicine Reactive Oxygen Species T-Box Domain Proteins Signal Transduction |
| Zdroj: | Molecular Medicine Reports |
| ISSN: | 1791-3004 1791-2997 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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