On the contribution of Tau phosphorylation to nuclear and cytoplasmic changes in human neuroblastoma cells

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dc.contributor.authorTabeshmehr, Parisa
dc.contributor.examiningcommitteeKarimi, Soheila (Physiology and Pathophysiology)
dc.contributor.examiningcommitteeLindsey, Benjamin (Human anatomy and cell science)
dc.contributor.supervisorEftekharpour, Eftekhar
dc.date.accessioned2023-08-10T18:58:10Z
dc.date.available2023-08-10T18:58:10Z
dc.date.issued2023-08-09
dc.date.submitted2023-08-09T17:37:08Zen_US
dc.degree.disciplinePhysiology and Pathophysiologyen_US
dc.degree.levelMaster of Science (M.Sc.)
dc.description.abstractHuman tauopathies are characterized by intracellular aggregation of hyperphosphorylated tau protein in neurons. Tau is involved in many cellular functions through its association with microtubules and actin filaments. In tauopathies overstabilization of filamentous actin (f-actin) leads to invagination of nuclear envelope. An intricate protein layer known as Nuclear Lamina (NL) is located at the interface of inner layers of nuclear envelope and chromatin. NL is degraded after nuclear envelope invagination, resulting in aberrant gene expression and re-emergence of ancient retroviruses. It is not clear if inhibition of kinases involved in tau pathology can prevent NL invagination and its downstream events. In this study, we first established that overexpression of full-length tau (FL-Tau) and the 35kDa C-terminal fragment (Tau35) in differentiated human neuroblastoma (dSH-SY5Y) cell lines enhanced nuclear lamina invagination and overstabilization of filamentous actin; however, these changes were significantly exacerbated in Tau35-overexpressing cells. Application of two small molecule inhibitors of c-Jun N-terminal kinase (JNK) and glycogen synthase kinase-3β (GSK-3β) reduced the extent of damages in tau-overexpressing cells. JNK inhibitor significantly decreased NL invagination in dSH-SY5Y-FL-Tau and -Tau35 cells. Furthermore, GSK-3β inhibition alleviated f-actin overstabilization in dSH-SY5Y-FL-Tau cells. In conclusion, we identified that NL invagination and f-actin overstabilization could be modulated by inhibition of involving kinases in tauopathies.
dc.description.noteOctober 2023
dc.identifier.urihttp://hdl.handle.net/1993/37452
dc.language.isoeng
dc.rightsopen accessen_US
dc.subjectTau
dc.subjectTauopathy
dc.subjectNeurodegeneration
dc.subjectAlzheimer’s Disease
dc.subjectDementia
dc.subjectAging
dc.subjectMAPT
dc.subjectCytoskeleton
dc.titleOn the contribution of Tau phosphorylation to nuclear and cytoplasmic changes in human neuroblastoma cells
dc.typemaster thesisen_US
local.subject.manitobano
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