A novel pathogenic Tau translocator from cytoplasm into the nucleus upon Neurodegeneration

Background and Aim : Tau hyperphosphorylation is an early event in several neurodegenerative diseases, known as tauopathies. However, the actual mechanism of Tau toxicity in neurons has remained elusive thus far. We have hypothesized that neurotoxic Cis p-Tau initially interacts with specific translocator (importin), then moves into the nucleus, resulting in cell death. Thus, we hypothesised that importin suppression would prevent the cell death.Methods : To examine how Cis p-Tau is being imported into the nucleus, we initially determined the translocation time-frames using immunoflourescent staining on pri mary cultured neurons. Then, we blocked the Importin using 5μM Ivermectin, as Importin inhibitor, and examined cell viabilities.Results : We found that pathogenic Cis p-Tau bound to Importin, and then moved into the nucleus in a ti me-dependent manner. Notably, Importin suppression would rescue neurodegeneration in those stressed out neurons.Conclusion : We have shown that Cis p-Tau plays its neurotoxcic roles through interacting with Importin. Taking these together, we herein describe tauopathies molecular mechanism and a novel therapeutic target for suppressing neuronal cell death upon neurodegenerative disorders such as: Alzheimer’s disease.

Keywords:

Cis p-Tau , Tauopathy , Neurodegeneration , Importin