Impact of frameshifting on aggregation of huntingtin exon 1:
Gespeichert in:
| 1. Verfasser: | |
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| Format: | Abschlussarbeit Buch |
| Sprache: | English |
| Veröffentlicht: |
2012
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| Schlagworte: | |
| Online-Zugang: | Inhaltsverzeichnis |
| Beschreibung: | VII, 145 S. Ill., graph. Darst. |
Internformat
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Datensatz im Suchindex
| _version_ | 1804151470290894848 |
|---|---|
| adam_text | CONTENTS
ACKNOWLEDGEMENTS VI
ABSTRACT VII
1 INTRODUCTION 1
1.1 MISFOLDING DISEASES AND AMYLOID FORMATION 1
1.2 POLYGLUTAMINE DISEASES 6
1.2.1 POLYGLUTAMINE DISEASE PATHOLOGY 6
1.2.2 AGGREGATION OF POLYGLUTAMINE PROTEINS 7
1.2.2.1 AGGREGATION OF POLYGLUTAMINE PEPTIDES 7
1.2.2.2 AGGREGATION IN THE PROTEIN CONTEXT 9
1.2.2.3 AGGREGATION IN THE CELL 10
1.2.2.4 THE ROLE OF AGGREGATION IN PATHOGENESIS 12
1.3 HUNTINGTON S DISEASE 14
1.3.1 HUNTINGTON S DISEASE PATHOLOGY 14
1.3.2 HUNTINGTIN 16
1.3.3 AGGREGATION OF MUTANT HUNTINGTIN 17
1.4 POLY
ALANINE DISORDERS 19
1.4.1 AGGREGATION OF POLYADENYLATE-BINDING PROTEIN, NUCLEAR 1 . 21
1.5 POLYALANINE PROTEINS IN THE CONTEXT OF POLYGLUTAMINE DISEASES ... 22
2 AIM OF THE THESIS 24
3 MATERIALS AND METHODS 26
3.1 MATERIALS 26
3.1.1 ANTIBODIES 26
3.1.2 CELL CULTURE REAGENTS 27
3.1.3 CELL STRAINS 28
3.1.4 CHEMICALS 28
3.1.5 ENZYMES 30
3.1.6 PLASMIDS 30
I
HTTP://D-NB.INFO/1043383948
CONTENTS
3.1.7 PRIMERS 32
3.2 METHODS 33
3.2.1 MOLECULAR BIOLOGICAL METHODS 33
3.2.2 BIOCHEMICAL AND BIOPHYSICAL METHODS 36
3.2.3 CELL CULTURE 41
3.3 FREQUENTLY USED BUFFERS AND MEDIA 43
4 RESULTS 46
4.1 A NOTE ON NOMENCLATURE 46
4.2 IDENTIFICATION OF HTT FRAMESHIFTED SPECIES IN A NEURONAL MODEL ...
47
4.2.1 REPORTER-ASSAY DESIGN 47
4.2.2 IDENTIFICATION OF FRAMESHIFTED PROTEINS BY WESTERN-BLOT . . 48
4.2.3 IDENTIFICATION OF FRAMESHIFTED PROTEINS BY MALDI-MS . . 54
4.3 IN VIVO MORPHOLOGY OF FRAMESHIFTED PROTEIN AGGREGATES 57
4.4 !N VIVO IMPACT OF HTTQ/A PROTEINS ON HTTPOLYQ AGGREGATION .... 61
4.5 IN VITRO INVESTIGATION OF HTTQ/A PROTEINS 64
4.5.1 HTTQ/A LIBRARY DESIGN 64
4.5.2 IN VITRO AGGREGATION OF HTTQ/A PROTEINS 67
4.5.2.1 TEM ANALYSIS 67
4.5.2.2 CD AND SDS-RESISTANCE ANALYSIS 68
4.5.2.3 LONG-TERM AGGREGATION ANALYSIS 74
4.6 IN VITRO IMPACT OF HTTQ/A PROTEINS ON HTTPOLYQ AGGREGATION . ... 78
4.6.1 AGGREGATION OF HTT52Q 78
4.6.2 INFLUENCE OF HTTQ/A PROTEINS ON HTT52Q 83
5 DISCUSSION 90
5.1 FRAMESHIFTING IN THE CELLULAR CONTEXT 90
5.2 IN VITRO INFLUENCE OF FRAMESHIFTED PROTEINS 93
5.2.1 AGGREGATION OF HTTQ/A PROTEINS 93
5.2.2 AGGREGATION OF HTT52Q 94
5.2.3 A STRUCTURAL MODEL HOW HTTQ/A PROTEINS IMPACT HTTPOLYQ
AGGREGATION 95
5.3 FUTURE PERSPECTIVES 98
REFERENCES 100
6 APPENDIX 128
6.1 ABBREVIATIONS 128
6.2 PROTEIN SEQUENCES 130
6.2.1 PROTEIN SEQUENCES USED IN IN VITRO WORK 130
6.2.2 PROTEIN SEQUENCES USED IN IN VIVO WORK 132
II
CONTENTS
6.3 SUPPLEMENTARY FIGURES 134
6.3.1 IN VIVO RESULTS 134
6.3.2 IN VITRO RESULTS 135
DECLARATION OF AUTHORSHIP 145
III
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| spelling | Girstmair, Hannah Verfasser aut Impact of frameshifting on aggregation of huntingtin exon 1 von Hannah Girstmair 2012 VII, 145 S. Ill., graph. Darst. txt rdacontent n rdamedia nc rdacarrier Potsdam, Univ., Diss., 2012 (DE-588)4113937-9 Hochschulschrift gnd-content DNB Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=026824909&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
| spellingShingle | Girstmair, Hannah Impact of frameshifting on aggregation of huntingtin exon 1 |
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| title | Impact of frameshifting on aggregation of huntingtin exon 1 |
| title_auth | Impact of frameshifting on aggregation of huntingtin exon 1 |
| title_exact_search | Impact of frameshifting on aggregation of huntingtin exon 1 |
| title_full | Impact of frameshifting on aggregation of huntingtin exon 1 von Hannah Girstmair |
| title_fullStr | Impact of frameshifting on aggregation of huntingtin exon 1 von Hannah Girstmair |
| title_full_unstemmed | Impact of frameshifting on aggregation of huntingtin exon 1 von Hannah Girstmair |
| title_short | Impact of frameshifting on aggregation of huntingtin exon 1 |
| title_sort | impact of frameshifting on aggregation of huntingtin exon 1 |
| topic_facet | Hochschulschrift |
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