| Abbreviations | 第7-9页 |
| Chinese Abstract | 第9-13页 |
| English Abstract | 第13页 |
| Introduction | 第18-43页 |
| 1． Prion diseases | 第18-20页 |
| 2． Prion proteins（PrP） | 第20-22页 |
| 3． Studies on cellular prion protein（PrPc） | 第22-43页 |
| 3．1 Localization of PrPc in CNS | 第22-23页 |
| 3．2 Insights into the physiological functions of PrPc | 第23-31页 |
| 3．2．1 PrP-deleted animals | 第24-27页 |
| 3．2．2 PrPc as a copper uptake protein | 第27-29页 |
| 3．2．3 PrPc in neuronal survival and differentiation | 第29-30页 |
| 3．2．4 PrPc and signal transduction | 第30-31页 |
| 3．3 PrPc-binding proteins | 第31-39页 |
| 3．3．1 Cell surface receptors | 第32-35页 |
| 3．3．2 Molecular chaperones | 第35-36页 |
| 3．3．3 Other PrP interacting molecules | 第36-39页 |
| 3．4 Therapeutics for prion diseases | 第39-43页 |
| 3．4．1 Polyanions | 第40-41页 |
| 3．4．2 Congo red | 第41页 |
| 3．4．3 Polyene antibiotics | 第41-42页 |
| 3．4．4 Antibodies | 第42-43页 |
| Materials | 第43-48页 |
| 1． Chemicals | 第43-45页 |
| 2． Equipment | 第45页 |
| 3． Other materials | 第45-48页 |
| 3．1 cDNA libraries | 第45-46页 |
| 3．2 plasmid DNAs | 第46页 |
| 3．3 Cell lines | 第46页 |
| 3．4 Antibodies | 第46-48页 |
| Part 1 Searching for binding molecules and binding sources for PrPc--cellular part | 第48-67页 |
| 1 Buffers and solutions | 第48-52页 |
| 2 Methods | 第52-58页 |
| 2．1 Construction and transformation of PrPAP | 第52页 |
| 2．2 Isolation of plasmid from E．Coli bacteria culture | 第52-53页 |
| 2．3 Selection of cell lines expressing high level of PrPAP after transient transfection | 第53-54页 |
| 2．4 ELISA of AP fusion proteins | 第54页 |
| 2．5 RAP in situ of mouse embryos | 第54-55页 |
| 2．6 Transient expression cloning | 第55-56页 |
| 2．7 Binding detection of PrPAP with adhesion molecules,cell lines and primary culture cells | 第56-58页 |
| 3 Results | 第58-62页 |
| 3．1 Selection of cell lines expressing high level of PrPAP after transient transfection | 第58页 |
| 3．2 RAP in situ of mouse embryos | 第58页 |
| 3．3 Transient expression cloning | 第58-59页 |
| 3．4 Adhesion molecules binding | 第59-62页 |
| 4 Discussion | 第62-67页 |
| 4．1 RAP in situ of mouse embryos and transient expression cloning | 第62-65页 |
| 4．2 Binding sources hunting | 第65-67页 |
| Part 2 Immunolocalization of the binding proteins for PrPc--morphological part | 第67-83页 |
| 1 Buffers and solutions | 第67-68页 |
| 2 Methods | 第68-74页 |
| 2．1 Construction of PrPFc | 第69页 |
| 2．2 Cell culture of transfected CHO-K1 cells | 第69页 |
| 2．3 Purification and concentration of PrPFc through Protein A affinity chromatography | 第69-70页 |
| 2．4 BCA protein assay | 第70-71页 |
| 2．5 SDS-PAGE,silver staining and Western blot | 第71页 |
| 2．6 Immunolocalization of the binding proteins for PrPc | 第71-74页 |
| 3 Results | 第74-78页 |
| 3．1 Purity and identity of the purified PrPFc | 第74页 |
| 3．2 Perfused animals-vibratome sections | 第74-75页 |
| 3．3 Living brain slices | 第75页 |
| 3．4 In vivo injection-vibratome sections | 第75页 |
| 3．5 Fresh frozen tissues-cryostat sections | 第75-78页 |
| 4 Discussion | 第78-83页 |
| Part 3 Differential gene expression in PrP knockout mice-PrP-related genes | 第83-91页 |
| 1 Buffers and solutions | 第83页 |
| 2 Methods | 第83-86页 |
| 2．1 Preparation of total RNA with RNeasy Maxi kit | 第83-84页 |
| 2．2 Poly A+ mRNA isolation from total RNA preparations using the Dynabeads mRNA Purification kit | 第84-85页 |
| 2．3 Hybridization of the arrayed genes with probes | 第85-86页 |
| 3 Results | 第86-87页 |
| 4 Discussion | 第87-91页 |
| Part 4． Identification and separation of PrPc binding partners--biochemical part | 第91-111页 |
| 1 Buffers and solutions | 第91-95页 |
| 2 Methods | 第95-101页 |
| 2．1 Different binding material preparations-enrichment of the binding source | 第96-98页 |
| 2．2 Procedures for isolation and identification of the binding partners for PrPc | 第98-101页 |
| 2．3 Identification of the binding partners | 第101页 |
| 3 Results | 第101-106页 |
| 3．1 Detection of the binding bands and getting closer to more enrichment of the binding material | 第101-103页 |
| 3．2 Isolation of bands of interest and protein sequencing | 第103页 |
| 3．3 Confirmation of hypothesized binding candidates | 第103-106页 |
| 4 Discussion | 第106-111页 |
| 4．1 The procedure for binding bands detection | 第106-107页 |
| 4．2 The procedure for preparing proteins of interest for sequencing | 第107-108页 |
| 4．3 Analysis of the sequencing result | 第108-111页 |
| References | 第111-122页 |
| Acknowledgement | 第122页 |
