Title Page
ABSTRACT
Contents
ABBREVIATIONS 10
INTRODUCTION 12
MATERIALS AND METHODS 20
RESULTS 27
DISCUSSION 68
REFERENCES 72
국문 초록 86
Figure 1. Establishment and characterization of cell-based tau-BiFC propagation assay 39
Figure 2. Genome-wide functional screening of human secretome identified tau propagation modulators 41
Figure 3. TauSec treatment enhances tau propagation in neuronal cells. 43
Figure 4. TauSec promotes tau internalization in SH-SY5Y and mouse primary cortical neurons. 45
Figure 5. TauSec expression is increased in primary cortical neurons under various stress conditions. 47
Figure 6. TauSec increases the amount and modification of TauSec receptor 49
Figure 7. TauSec receptor is essential in TauSec mediatedtau internalization 51
Figure 8. TauSec-TauSec receptor interaction is important for tau uptake than TauSec's protease activity 53
Figure 9. Prolonged exposure to TauSec causes tau accumulation in neuronal cells 55
Figure 10. TauSec increases lysosomal pH. 57
Figure 11. Anti-TauSec receptor antibody blocks TauSec-mediated tau uptake. 59
Figure 12. TauSec/TauSec receptor PPI compound inhibits the interaction between TauSec and TauSec receptor 61
Figure 13. TauSec/TauSec receptor-PPI inhibits TauSec-mediated tau propagation and accumulation. 64
Figure 14. Schematic image of the role of TauSec in tau propagation 66