Cholesterol transfer at ER-endosome contact sites and α-synuclein clearance:
Gespeichert in:
| 1. Verfasser: | |
|---|---|
| Format: | Abschlussarbeit Buch |
| Sprache: | English |
| Veröffentlicht: |
Aachen
[2020]
|
| Schlagworte: | |
| Online-Zugang: | Inhaltsverzeichnis Inhaltsverzeichnis |
| Beschreibung: | 83 Seiten Illustrationen, Diagramme 21 cm |
Internformat
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| 100 | 1 | |a Gorzel, Karolina Marta |d 1995- |e Verfasser |0 (DE-588)1218089822 |4 aut | |
| 245 | 1 | 0 | |a Cholesterol transfer at ER-endosome contact sites and α-synuclein clearance |c vorgelegt von Karolina Marta Gorzel |
| 264 | 1 | |a Aachen |c [2020] | |
| 300 | |a 83 Seiten |b Illustrationen, Diagramme |c 21 cm | ||
| 336 | |b txt |2 rdacontent | ||
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| 502 | |b Dissertation |c RWTH Aachen |d 2020 | ||
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Datensatz im Suchindex
| _version_ | 1804182893351665664 |
|---|---|
| adam_text | TABLE
OF
CONTENTS
ABBREVIATIONS
1
INTRODUCTION
..........................................................................................................
1
1.1
PARKINSON
*
S
DISEASE
......................................................................................
1
1.1.1
EPIDEMIOLOGY
....................................................................................................
1
1.1.2
CLINICAL
MANIFESTATION
.......................................................................................
1
1.1.3
ETIOLOGY
.............................................................................................................
3
1.1.4
NEUROPATHOLOGICAL
HALLMARKS
...........................................................................
5
1.1.5
BASAL
GANGLIA
PATHOPHYSIOLOGY
........................................................................
6
1.1.6
THERAPEUTIC
APPROACHES
..................................................................................
7
1.2
AUTOPHAGY
.........................................................................................................
8
1.3
MEMBRANE
CONTACT
SITES
.............................................................................
9
1.3.1
FUNCTION
OF
MEMBRANE
CONTACT
SITES
.............................................................
9
1.3.2
MICROTUBULES
AND
RAB7
................................................................................
10
1.3.3
CONTACT
SITE
PROTEINS
.....................................................................................
11
1.3.4
CHOLESTEROL
.....................................................................................................
15
2
AIMS
AND
OBJECTIVES
..........................................................................................
19
3
MATERIALS
AND
METHODS
..................................................................................
20
3.1
MATERIALS
................................................................................................................
20
3.2
CELL
CULTURE
AND
TRANSFECTION
................................................................................
20
3.3
IMMUNOFLUORESCENCE
............................................................................................
21
3.4
CHOLESTEROL
DEPLETION
AND
ENRICHMENT
................................................................
21
3.5
PARTICLE
COUNTING
AND
ANALYSIS
.............................................................................
22
3.6
TIME-LAPSE
MICROSCOPY
........................................................................................
22
3.7
STATISTICAL
ANALYSIS
................................................................................................
23
4
RESULTS
....................................................................................................................
24
4.1
EFFECTS
OF
ENDOGENOUS
AND
EXOGENOUS
CHOLESTEROL
ON
VIABILITY
AND
AGGREGATE
CLEARANCE
........................................................................................................................
24
4.1.1
IMPAIRED
ENDOGENOUS
CHOLESTEROL
SYNTHESIS
DOES
NOT
IMPAIR
RAB7
FUNCTIONING
..................................................................................................................
24
4.1.2
EXOGENOUS
CHOLESTEROL
SUPPLY
IS
PREVENTED
BY
THE
USE
OF
SERUM
FREE
MEDIUM
.......................................................................................................................
25
4.1.3
RAB7
FUNCTIONING
IS
REQUIRED
FOR
CELL
VIABILITY
...............................................
25
4.1.4
CHOLESTEROL
ADDITION
PROMOTES
AGGREGATE
CLEARANCE
...................................
27
4.1.5
LOW
ER
CHOLESTEROL
PROMOTES
FYCO1-MEDIATED
TRANSPORT
.........................
31
4.2
EFFECT
OF
STEROL
DEPLETION
ON
PARTICLE
TRANSPORT
....................................................
33
4.2.1
SIMVASTATIN
INHIBITS
MOBILITY
OF
AUTOPHAGIC
VESICLES
...................................
33
4.2.2
SIMVASTATIN
INHIBITS
MOBILITY
OF
ALPHA-SYNUCLEIN
PARTICLES
............................
34
4.2.3
CHOLESTEROL
DEPLETION
INHIBITS
MATURATION,
NOT
FUSION
...................................
36
4.3
ROLE
OF
CONTACT
SITES
IN
FUSION
AND
MATURATION
....................................................
37
4.3.1
CONTACT
SITES
ARE
REQUIRED
FOR
FUSION
...........................................................
37
4.3.2
VAP-A
DEFICIENCY
DOES
NOT
IMPAIR
RAB7
FUNCTION
........................................
38
4.3.3
RAB7
FUNCTIONING
IS
LINKED
TO
VAP-A
.............................................................
39
4.4
ROLE
OF
SPECIFIC
CONTACT
SITE
ADAPTORS
FOR
AGGREGATE
CLEARANCE
AND
VESICLE
MOVEMENT
.......................................................................................................................
40
4.4.1
ORP1L
IN
TRANSPORT
AND
SYNUCLEIN
CLEARANCE
...............................................
40
4.4.2
THE
ROLE
OF
ORP5
IN
TRANSPORT
AND
SYNUCLEIN
CLEARANCE
..............................
48
4.4.3
INFLUENCE
OF
NPC1
ON
ER-ENDOSOME
CONTACT
SITES
.....................................
54
4.4.4
ROLE
OF
STARD3-MEDIATED
ER
TO
ENDOSOME
CHOLESTEROL
TRANSPORT
ON
AGGREGATE
CLEARANCE
..................................................................................................
55
5
DISCUSSION
.............................................................................................................
57
5.1
LOW
ER
CHOLESTEROL
IMMOBILIZES
PARTICLES
..........................................................
57
5.2
CHOLESTEROL
GRADIENTS
DETERMINE
THE
DIRECTION
OF
ENDOSOME
TRANSPORT
............
58
5.3
BLOCKING
ENDOGENOUS
CHOLESTEROL
SYNTHESIS
REVERSES
THE
DIRECTION
OF
TRANSPORT
59
5.4
AUTOPHAGOSOMES
ARE
NOT
INFLUENCED
BY
CHOLESTEROL
GRADIENTS
..........................
62
5.5
CHOLESTEROL
AFFECTS
LYSOSOMAL
ACIDIFICATION
AND
FUSION
VIA
RAB7
.......................
63
5.6
ORP5
INFLUENCES
TRANSPORT
VIA
MULTIPLE
PATHWAYS
.............................................
63
5.7
RAB7
INDUCES
TRANSPORT
OF
LNAVS
TO
THE
CELL
CENTER
..........................................
64
5.8
CHOLESTEROL
OVERLOAD
PREVENTS
CLEARANCE
...........................................................
64
5.9
CHOLESTEROL
AND
ALPHA-SYNUCLEIN
AGGREGATION
....................................................
66
5.10
CONCLUSION
.........................................................................................................
66
5.11
OUTLOOK
...............................................................................................................
67
6
ABSTRACT
................................................................................................................
68
7
REFERENCES
...........................................................................................................
70
ACKNOWLEDGEMENTS
...............................................................................................
80
DECLARATION
................................................................................................................
81
CURRICULUM
VITAE
......................................................................................................
83
|
| adam_txt |
TABLE
OF
CONTENTS
ABBREVIATIONS
1
INTRODUCTION
.
1
1.1
PARKINSON
*
S
DISEASE
.
1
1.1.1
EPIDEMIOLOGY
.
1
1.1.2
CLINICAL
MANIFESTATION
.
1
1.1.3
ETIOLOGY
.
3
1.1.4
NEUROPATHOLOGICAL
HALLMARKS
.
5
1.1.5
BASAL
GANGLIA
PATHOPHYSIOLOGY
.
6
1.1.6
THERAPEUTIC
APPROACHES
.
7
1.2
AUTOPHAGY
.
8
1.3
MEMBRANE
CONTACT
SITES
.
9
1.3.1
FUNCTION
OF
MEMBRANE
CONTACT
SITES
.
9
1.3.2
MICROTUBULES
AND
RAB7
.
10
1.3.3
CONTACT
SITE
PROTEINS
.
11
1.3.4
CHOLESTEROL
.
15
2
AIMS
AND
OBJECTIVES
.
19
3
MATERIALS
AND
METHODS
.
20
3.1
MATERIALS
.
20
3.2
CELL
CULTURE
AND
TRANSFECTION
.
20
3.3
IMMUNOFLUORESCENCE
.
21
3.4
CHOLESTEROL
DEPLETION
AND
ENRICHMENT
.
21
3.5
PARTICLE
COUNTING
AND
ANALYSIS
.
22
3.6
TIME-LAPSE
MICROSCOPY
.
22
3.7
STATISTICAL
ANALYSIS
.
23
4
RESULTS
.
24
4.1
EFFECTS
OF
ENDOGENOUS
AND
EXOGENOUS
CHOLESTEROL
ON
VIABILITY
AND
AGGREGATE
CLEARANCE
.
24
4.1.1
IMPAIRED
ENDOGENOUS
CHOLESTEROL
SYNTHESIS
DOES
NOT
IMPAIR
RAB7
FUNCTIONING
.
24
4.1.2
EXOGENOUS
CHOLESTEROL
SUPPLY
IS
PREVENTED
BY
THE
USE
OF
SERUM
FREE
MEDIUM
.
25
4.1.3
RAB7
FUNCTIONING
IS
REQUIRED
FOR
CELL
VIABILITY
.
25
4.1.4
CHOLESTEROL
ADDITION
PROMOTES
AGGREGATE
CLEARANCE
.
27
4.1.5
LOW
ER
CHOLESTEROL
PROMOTES
FYCO1-MEDIATED
TRANSPORT
.
31
4.2
EFFECT
OF
STEROL
DEPLETION
ON
PARTICLE
TRANSPORT
.
33
4.2.1
SIMVASTATIN
INHIBITS
MOBILITY
OF
AUTOPHAGIC
VESICLES
.
33
4.2.2
SIMVASTATIN
INHIBITS
MOBILITY
OF
ALPHA-SYNUCLEIN
PARTICLES
.
34
4.2.3
CHOLESTEROL
DEPLETION
INHIBITS
MATURATION,
NOT
FUSION
.
36
4.3
ROLE
OF
CONTACT
SITES
IN
FUSION
AND
MATURATION
.
37
4.3.1
CONTACT
SITES
ARE
REQUIRED
FOR
FUSION
.
37
4.3.2
VAP-A
DEFICIENCY
DOES
NOT
IMPAIR
RAB7
FUNCTION
.
38
4.3.3
RAB7
FUNCTIONING
IS
LINKED
TO
VAP-A
.
39
4.4
ROLE
OF
SPECIFIC
CONTACT
SITE
ADAPTORS
FOR
AGGREGATE
CLEARANCE
AND
VESICLE
MOVEMENT
.
40
4.4.1
ORP1L
IN
TRANSPORT
AND
SYNUCLEIN
CLEARANCE
.
40
4.4.2
THE
ROLE
OF
ORP5
IN
TRANSPORT
AND
SYNUCLEIN
CLEARANCE
.
48
4.4.3
INFLUENCE
OF
NPC1
ON
ER-ENDOSOME
CONTACT
SITES
.
54
4.4.4
ROLE
OF
STARD3-MEDIATED
ER
TO
ENDOSOME
CHOLESTEROL
TRANSPORT
ON
AGGREGATE
CLEARANCE
.
55
5
DISCUSSION
.
57
5.1
LOW
ER
CHOLESTEROL
IMMOBILIZES
PARTICLES
.
57
5.2
CHOLESTEROL
GRADIENTS
DETERMINE
THE
DIRECTION
OF
ENDOSOME
TRANSPORT
.
58
5.3
BLOCKING
ENDOGENOUS
CHOLESTEROL
SYNTHESIS
REVERSES
THE
DIRECTION
OF
TRANSPORT
59
5.4
AUTOPHAGOSOMES
ARE
NOT
INFLUENCED
BY
CHOLESTEROL
GRADIENTS
.
62
5.5
CHOLESTEROL
AFFECTS
LYSOSOMAL
ACIDIFICATION
AND
FUSION
VIA
RAB7
.
63
5.6
ORP5
INFLUENCES
TRANSPORT
VIA
MULTIPLE
PATHWAYS
.
63
5.7
RAB7
INDUCES
TRANSPORT
OF
LNAVS
TO
THE
CELL
CENTER
.
64
5.8
CHOLESTEROL
OVERLOAD
PREVENTS
CLEARANCE
.
64
5.9
CHOLESTEROL
AND
ALPHA-SYNUCLEIN
AGGREGATION
.
66
5.10
CONCLUSION
.
66
5.11
OUTLOOK
.
67
6
ABSTRACT
.
68
7
REFERENCES
.
70
ACKNOWLEDGEMENTS
.
80
DECLARATION
.
81
CURRICULUM
VITAE
.
83 |
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| genre | (DE-588)4113937-9 Hochschulschrift gnd-content |
| genre_facet | Hochschulschrift |
| id | DE-604.BV047564694 |
| illustrated | Illustrated |
| index_date | 2024-07-03T18:28:15Z |
| indexdate | 2024-07-10T09:14:47Z |
| institution | BVB |
| language | English |
| oai_aleph_id | oai:aleph.bib-bvb.de:BVB01-032940072 |
| oclc_num | 1245376394 |
| open_access_boolean | |
| owner | DE-355 DE-BY-UBR |
| owner_facet | DE-355 DE-BY-UBR |
| physical | 83 Seiten Illustrationen, Diagramme 21 cm |
| publishDate | 2020 |
| publishDateSearch | 2020 |
| publishDateSort | 2020 |
| record_format | marc |
| spelling | Gorzel, Karolina Marta 1995- Verfasser (DE-588)1218089822 aut Cholesterol transfer at ER-endosome contact sites and α-synuclein clearance vorgelegt von Karolina Marta Gorzel Aachen [2020] 83 Seiten Illustrationen, Diagramme 21 cm txt rdacontent n rdamedia nc rdacarrier Dissertation RWTH Aachen 2020 (DE-588)4113937-9 Hochschulschrift gnd-content B:DE-101 application/pdf https://d-nb.info/1225499585/04 Inhaltsverzeichnis DNB Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=032940072&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis 1\p aepgnd 0,16326 20210303 DE-101 https://d-nb.info/provenance/plan#aepgnd |
| spellingShingle | Gorzel, Karolina Marta 1995- Cholesterol transfer at ER-endosome contact sites and α-synuclein clearance |
| subject_GND | (DE-588)4113937-9 |
| title | Cholesterol transfer at ER-endosome contact sites and α-synuclein clearance |
| title_auth | Cholesterol transfer at ER-endosome contact sites and α-synuclein clearance |
| title_exact_search | Cholesterol transfer at ER-endosome contact sites and α-synuclein clearance |
| title_exact_search_txtP | Cholesterol transfer at ER-endosome contact sites and α-synuclein clearance |
| title_full | Cholesterol transfer at ER-endosome contact sites and α-synuclein clearance vorgelegt von Karolina Marta Gorzel |
| title_fullStr | Cholesterol transfer at ER-endosome contact sites and α-synuclein clearance vorgelegt von Karolina Marta Gorzel |
| title_full_unstemmed | Cholesterol transfer at ER-endosome contact sites and α-synuclein clearance vorgelegt von Karolina Marta Gorzel |
| title_short | Cholesterol transfer at ER-endosome contact sites and α-synuclein clearance |
| title_sort | cholesterol transfer at er endosome contact sites and α synuclein clearance |
| topic_facet | Hochschulschrift |
| url | https://d-nb.info/1225499585/04 http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=032940072&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
| work_keys_str_mv | AT gorzelkarolinamarta cholesteroltransferaterendosomecontactsitesandasynucleinclearance |
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