Title Page
Contents
ABSTRACT 11
1. Introduction 14
1.1. Complement system 14
1.2. Macroglobulin complement-related 16
1.3. Complement system and autophagy 21
1.4. Complement system and Aβ pathology 21
1.5. Aim of this study 22
2. Materials and Methods 23
2.1. Drosophila strain 23
2.2. cDNA synthesis and RT-qPCR 23
2.3. Immunohistochemistry 24
2.4. Thioflavin S staining 24
2.5. Brain section and hematoxylin and eosin staining 25
2.6. Quantitative of GFP-mCherry-Atg8a puncta 25
2.7. Analysis of Drosophila locomotor activity 26
2.8. Measurement of fly lifespan 26
2.9. Statistics 26
3. Results 27
3.1. Mcr expression in the Drosophila central nervous system 27
3.2. Expression of Mcr is reduced in Drosophila model of AD 28
3.3. Neuron-specific overexpression of Mcr alleviates Aβ-induced neurodegeneration in Drosophila model of AD 28
3.4. Neuron-specific overexpression of Mcr alleviates Aβ accumulation and aggregation in Drosophila model of AD 30
3.5. Neuron-specific overexpression of Mcr does not affect the aggregation of ubiquitinated proteins in Drosophila model of AD 31
3.6. Neuron-specific regulation of Mcr affects glial cell number in Drosophila model of AD 31
3.7. Neuron-specific regulation of Mcr affects autophagy in Drosophila model of AD 32
3.8. Neuron-specific regulation of Mcr does not affect locomotor activity and lifespan in Drosophila model of AD 33
4. Discussion 54
References 58
ABSTRACT(in Korean) 67
Table 1. Neuron-specific regulation of Mcr does not affect lifespan in Drosophila model of AD. 56
Figure 1. Function of complement system. 16
Figure 2. Sequence alignment of Mcr and mammalian complement factors. 20
Figure 3. Mcr mRNA expression in the Drosophila brain. 34
Figure 4. Mcr mRNA expression in Drosophila neurons and glia cells during aging. 35
Figure 5. Mcr mRNA levels in Mcr mutants. 36
Figure 6. Mcr mRNA levels in Drosophila model of AD. 37
Figure 7. Effects of neuron-specific Mcr regulation on Aβ-induced neuronal cell death in Drosophila model of AD. 39
Figure 8. Effects of neuron-specific Mcr regulation on Aβ-induced neurodegeneration in Drosophila model of AD. 40
Figure 9. Effects of neuron-specific Mcr regulation on Aβ accumulation in Drosophila model of AD. 42
Figure 10. Effects of neuron-specific Mcr regulation on Aβ aggregation in Drosophila model of AD. 44
Figure 11. Effects of neuron-specific Mcr regulation on aggregation of ubiquitinated proteins in Drosophila model of AD. 46
Figure 12. Effects of neuron-specific Mcr expression on glial cells in Drosophila model of AD. 48
Figure 13. Effects of neuron-specific Mcr regulation on autophagy in Drosophila model of AD. 51
Figure 14. Effects of neuron-specific Mcr regulation on locomotor activity in Drosophila model of AD. 52
Figure 15. Effects of neuron-specific Mcr regulation on lifespan in Drosophila model of AD. 53