Title Page
Contents
ABSTRACT 8
1. Introduction 10
1.1. Myokine 10
1.2. Myokine and Alzheimer disease 11
1.3. Bioinformatic approaches to myokine 12
1.4. Aims 13
2. Materials and Methods 15
2.1. Drosophila strains 15
2.2. Preparing Drosophila for screening 18
2.3. Immunohistochemistry 18
2.4. Statistical analysis 19
2.5. Categorizing myokines used in screening 19
3. Results 21
3.1. Screening for myokines that affect Aβ accumulation in the Drosophila AD model brain 21
3.2. Categorization of genes used in the screening and selection of Alzheimer disease-relevant categories 27
3.2.1. Wnt pathway 28
3.2.2. Extracellular matrix 29
3.2.3. Developmental process 30
3.2.4. Cytokine activity 31
4. Discussion 42
References 47
Abstract (in Korean) 53
Table 1. List of Drosophila lines used in this screening. 17
Table 2. Classification of genes selected as a result of screening. 32
Figure 1. Hypothesis underlying the screening. 14
Figure 2. A genetic scheme for generating Drosophila model of Alzheimer disease in which the levels of a myokine have been... 23
Figure 3. Aβ accumulation in the brain of a Drosophila model of AD. 24
Figure 4. Screening result of myokines affecting Aβ accumulation in the brain of a Drosophila model of Alzheimer disease. 26
Figure 5. Knockdown of Wnt pathway category genes effectively affects Aβ aggregation. 35
Figure 6. Knockdown of extracellular matrix genes effectively affects Aβ aggregation. 37
Figure 7. Knockdown of genes involved in developmental process has a significant effect on Aβ aggregation. 39
Figure 8. Knockdown of genes involved in cytokine category significantly affects Aβ aggregation. 41