Die Rolle des Signal Transducer and Activator of Transcription 3 (STAT3) bei der axonalen Regeneration im zentralen Nervensystem:
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| Format: | Thesis Book |
| Language: | English |
| Published: |
2013
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| Subjects: | |
| Online Access: | Volltext http://d-nb.info/1033504637/34 https://nbn-resolving.org/urn:nbn:de:bvb:19-155683 Inhaltsverzeichnis |
| Physical Description: | X, 105 S. Ill., graph. Darst. |
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| 245 | 1 | 0 | |a Die Rolle des Signal Transducer and Activator of Transcription 3 (STAT3) bei der axonalen Regeneration im zentralen Nervensystem |c Natalie Garzorz |
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Record in the Search Index
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| adam_text | IMAGE 1
TABLE OF CONTENTS
L
TABLE OF CONTENTS
TABLE OF CONTENTS I
LIST OF FIGURES III
LISTOFTABLES III
LIST OF ABBREVIATIONS IV
ZUSAMMENFASSUNG .VII
SUMMARY IX
1 INTRODUCTION 1
1.1 EPIDEMIOLOGY, ETIOLOGY AND CLINICAL PICTURE OF SPINAL CORD INJURY 1
1.2 PATHOPHYSIOLOGY AND DINICAL MANAGEMENT OF SCI 2
1.3 PREDINICAL AND DINICAL TRIALS IN THE FIELD OF SCI 3
1.4 THE FAILURE OF SUCCESSFUL AXONAL REGENERATION IN THE CENTRAL NERVOUS
SYSTEM 5 1.4.1 THE GROWTH INHIBITORY CNS ENVIRONMENT 6
1.4.2 THE INSUFFICIENT ACTIVATION OF THE INTRINSIC NEURONAL GROWTH
PROGRAM UPON INJURY IN THE CNS 8
1.5 STAT3 17
1.5.1 THESTATFAMILY 17
1.5.2 THE JAK/STAT PATHWAY 18
1.5.3 THE ROLE OF STAT3 OUTSIDE THE NERVOUS SYSTEM 20
1.5.4 STAT3 IN THE CONTEXT OF NEURONAL SURVIVAL AND REGENERATION 22 1.6
RESEARCH QUESTION 24
2 MATERIAL AND METHODS 25
2.1 MATERIAL 25
2.2 MICE..; : 30
2.3 METHODS 31
2.3.1 PLASMID CONSTRUCTS 31
2.3.2 VECTOR PRODUCTION AND PURIFICATION 31
2.3.3 TISSUE PROCESSING AND IMMUNOHISTOCHEMISTRY 32
2.3.4 QUANTIFICATION OF THE EXPRESSION OF P-STAT3 AND STAT3 33
2.3.5 GENE THERAPY WITH RECOMBINANT ADENO-ASSOCIATED VIRAL VECTORS 33
2.3.6 CONFOCAL MICROSCOPY 34
2.3.7 IN SITU ANALYSIS OF CENTRAL AXONAL OUTGROWTH 34
2.3.8 IN VIVO ANALYSIS OF CENTRAL.AXONAL OUTGROWTH 4 1
2.3.9 COMBINATION THERAPY WITH VIRAL GENE TRANSFER AND CHONDROITINASE
ABC 4 1 2.3.10 . STATISTICAL ANALYSIS 42
3 EXPERIMENTS IN THE COURSE OF THIS STUDY PRIOR TO MY OWN WORK 44
STAT3 DEPLETION IMPAIRS THE REGENERATION OF PNS AXONS 44
STAT3 DELETION IMPAIRS INITIATION BUT NOT PERPETUATION OF PNS AXON
REGENERATION IN VIVO 44 4 RESULTS 45
4.1 CONSEQUENCES OF A PERIPHERAL CRUSH LESION ON STAT3 EXPRESSION 45 4.2
STAT3 EXPRESSION AFTER DORSAL COLUMN LESION 47
4.3 EFFICIENCY OF THE VIRAL GENE THERAPY 48
4.4 EFFECTS OF VIRAL GENE THERAPY WITH STAT3(C) ON AXON OUTGROWTH AFTER
CNS LESION .. 51 4.5 THE PHASE-SPECIFIC ROLE OF STAT3 FOR AXON
REGENERATION IN THE CNS 56
HTTP://D-NB.INFO/1035484668
IMAGE 2
TABLE OF CONTENTS II
4.6 EFFECTS OF STAT3 DELETION ON AXONAL OUTGROWTH AFTER CNS LESION 59
4.7 COMBINATION THERAPY WITH RAAV-STAT3 AND CHONDROITINASE ABC FOR
CENTRAL AXON REGENERATION 62
5 DISCUSSION 67
5.1 STAT3 IS A KEY COMPONENT OF THE INTRINSIC GROWTH PROGRAM 67
5.2 STAT3 IS AN INITIATOR OF NEURITE OUTGROWTH IN VIVO 68
5.3 STAT3 IS A PHASE-SPECIFIC REGULATOR OF AXONAL REGENERATION 73
5.4 STAT3 IS A PROMISING TARGET FOR THERAPEUTIC INTERVENTIONS 75
5.4.1 BEING IN THE RIGHT PLACE AT THE RIGHT TIME 76
5.4.2 IN SEARCHOFTHE IDEAL TARGET IN THE JAK/STAT PATHWAY 77
5.4.3 BRINGING STAT3 TO NEURONAL CELLS: MAXIMAL EFFICACY AND MINIMAL
SIDE EFFECTS.... 81 5.5 STAT3 IN COMBINATION WITH OTHER THERAPEUTIC
TARGETS 82
5.6 CONCLUDING REMARKS AND OUTLOOK 85
6 REFERENCES 89
7 ACKNOWLEDGMENTS 105
8 CURRICULUM VITAE 107
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| spelling | Garzorz, Natalie Verfasser aut Die Rolle des Signal Transducer and Activator of Transcription 3 (STAT3) bei der axonalen Regeneration im zentralen Nervensystem Natalie Garzorz 2013 X, 105 S. Ill., graph. Darst. txt rdacontent n rdamedia nc rdacarrier München, Univ., Diss., 2013 (DE-588)4113937-9 Hochschulschrift gnd-content Erscheint auch als Online-Ausgabe urn:nbn:de:bvb:19-155683 http://edoc.ub.uni-muenchen.de/15568/ Verlag kostenfrei Volltext http://d-nb.info/1033504637/34 Langzeitarchivierung Nationalbibliothek https://nbn-resolving.org/urn:nbn:de:bvb:19-155683 Resolving-System DNB Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=026050940&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
| spellingShingle | Garzorz, Natalie Die Rolle des Signal Transducer and Activator of Transcription 3 (STAT3) bei der axonalen Regeneration im zentralen Nervensystem |
| subject_GND | (DE-588)4113937-9 |
| title | Die Rolle des Signal Transducer and Activator of Transcription 3 (STAT3) bei der axonalen Regeneration im zentralen Nervensystem |
| title_auth | Die Rolle des Signal Transducer and Activator of Transcription 3 (STAT3) bei der axonalen Regeneration im zentralen Nervensystem |
| title_exact_search | Die Rolle des Signal Transducer and Activator of Transcription 3 (STAT3) bei der axonalen Regeneration im zentralen Nervensystem |
| title_full | Die Rolle des Signal Transducer and Activator of Transcription 3 (STAT3) bei der axonalen Regeneration im zentralen Nervensystem Natalie Garzorz |
| title_fullStr | Die Rolle des Signal Transducer and Activator of Transcription 3 (STAT3) bei der axonalen Regeneration im zentralen Nervensystem Natalie Garzorz |
| title_full_unstemmed | Die Rolle des Signal Transducer and Activator of Transcription 3 (STAT3) bei der axonalen Regeneration im zentralen Nervensystem Natalie Garzorz |
| title_short | Die Rolle des Signal Transducer and Activator of Transcription 3 (STAT3) bei der axonalen Regeneration im zentralen Nervensystem |
| title_sort | die rolle des signal transducer and activator of transcription 3 stat3 bei der axonalen regeneration im zentralen nervensystem |
| topic_facet | Hochschulschrift |
| url | http://edoc.ub.uni-muenchen.de/15568/ http://d-nb.info/1033504637/34 https://nbn-resolving.org/urn:nbn:de:bvb:19-155683 http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=026050940&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
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