The role of glycogen synthase kinase-3beta in alpha-synuclein-evoked tau phosphorylation

• Autorzy: Gassowska M. , Czapski G. A. , Adamczyk A.
• Języki publikacji: EN

Abstrakty

EN

Hyperphosphorylation of tau is involved in the pathomechanism of neurodegenerative disorders such as Alzheimer’s and Parkinson’s diseases. Recent studies suggested the significance of alpha-synuclein (ASN) in tau phosphorylation, however, the molecular mechanism responsible for ASN-mediated tau modification remains to be elucidated. In this study, we investigated the role of extracellular ASN in tau phosphorylation in PC12 dopaminergic cells and the involvement of glycogen synthase kinase-3 beta (GSK-3β) and cyclin-dependent kinase 5 (CDK5) in ASN-induced tau modification and cell death. We found that exogenously added ASN (10 µM) stimulates the phosphorylation of tau at Ser396 in PC12 cells. A specific GSK-3β inhibitor (SB-216763) prevented ASN-evoked tau hyperphosphorylation without effect of CDK5 inhibitors. Furthermore, we found that ASN enhanced of GSK-3β protein level and activity. Cell viability determined by MTT assay and Hoechst 33258 staining showed that ASN induced PC12 cell death that presented typical apoptotic morphology. SB-216763 prevented apoptotic cell death evoked by ASN. Concluding, extracellular ASN is involved in GSK-3β-dependent tau modulation and its proapoptotic effect might be mediated at least in part by GSK-3β-catalysed tau phosphorylation and cytoskeleton destabilisation. Supported by a grant from The National Science Centre 2012/05/B/NZ3/02047.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2013
• Tom: 73
• Numer: Suppl.1
• Opis fizyczny: p.53

Twórcy

autor

Gassowska M.

• Department of Cellular Signaling, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland

autor

Czapski G. A.

• Department of Cellular Signaling, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland

autor

Adamczyk A.

• Department of Cellular Signaling, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland