| dc.date.accessioned |
2021-11-17T08:55:04Z |
|
| dc.date.available |
2022-11-16T22:00:07Z |
|
| dc.date.issued |
2021-11-17 |
|
| dc.identifier.uri |
http://hdl.handle.net/123456789/38502 |
|
| dc.title |
ER-Mitochondria contact sites in stressed dopaminergic neurons – Implications for Parkinson’s disease |
en |
| ethesis.faculty |
Lääketieteellinen tiedekunta |
fi |
| ethesis.faculty |
Faculty of Medicine |
en |
| ethesis.faculty |
Medicinska fakulteten |
sv |
| ethesis.faculty.URI |
http://data.hulib.helsinki.fi/id/a4d5aaa2-b5aa-41a7-ba4c-e5e0df7a902d |
|
| ethesis.university.URI |
http://data.hulib.helsinki.fi/id/50ae46d8-7ba9-4821-877c-c994c78b0d97 |
|
| ethesis.university |
Helsingin yliopisto |
fi |
| ethesis.university |
University of Helsinki |
en |
| ethesis.university |
Helsingfors universitet |
sv |
| dct.creator |
Their, Anna |
|
| dct.issued |
2021 |
|
| dct.abstract |
The contact site between the endoplasmic reticulum and mitochondria, also known as the mitochondria endoplasmic reticulum contact sites (MERCS), have a crucial role in maintaining the homeostasis within the cell. Across the MERCS multiple functions, such as regulation of calcium (Ca2+) homeostasis, lipid metabolism, ER stress, mitochondrial quality control (MQC) and regulation of unfolded protein response (UPR) take place. These processes have been shown to be implicated in numerous different neurodegenerative diseases, such as Parkinson’s disease.
Parkinson’s disease is the second most common neurodegenerative disease that at the moment has no cure. The main obstacle in developing a neuroprotective treatment for the disease is the limited understanding of the key molecular events leading to neurodegeneration. One of the things in Parkinson’s disease that has eluded scientists for years is the selective death of the dopaminergic (DA) neurons in substantia nigra pars compacta. One hypothesis that could explain the selective death is the Ca2+ hypothesis, looking at the Ca2+ vulnerability of SNpc DA neurons as a plausible cause leading to the selective cell death. This project focused looking at the protein level and morphological changes of the ER and MERCS in stressed neurons, hypothesizing these as possible sites that contribute to the neuron vulnerability, as they are known to be the key modulators of the intracellular Ca2+ homeostasis.
This study looked closer at two MERC proteins, GRP75 and BAP31, and one ER protein, SERCA2, to see how they are affected in stressed dopamine-like neurons. Firstly, the in vitro model was established by differentiating SH-SY5Y neuroblastoma cells to dopamine-like neurons expressing tyrosine hydroxylase. Three different molecular compounds were tested as possible stressors affecting the Ca2+ homeostasis within the neurons, and we concluded that thapsigargin, a commonly used stressor to model PD like pathology, leads to the highest measurable ER Ca2+ depletion. Lastly, we quantitatively and qualitatively analyzed the effect of 24-hour treatment with each stressor on the differentiated SH-SY5Y neurons. Thapsigargin treatment lead to an increased level of GRP75 and SERCA2. A slight increase in BAP31 was also detected after thapsigargin treatment, but no apparent changes of the ER morphology were detected. The results, together with previous research, show GRP75 to be a possible contributor to the pathology of the disease, but further research is needed to see if it could be a possible target for treatment. |
en |
| dct.subject |
ER |
|
| dct.subject |
MERCS |
|
| dct.subject |
Parkinson's Disease |
|
| dct.subject |
calcium |
|
| dct.subject |
dopaminergic neurons |
|
| dct.subject |
SNpc |
|
| dct.subject |
SH-SY5Y |
|
| dct.subject |
GRP75 |
|
| dct.subject |
BAP31 |
|
| dct.subject |
SERCA2 |
|
| ethesis.language.URI |
http://data.hulib.helsinki.fi/id/languages/eng |
und |
| ethesis.language |
englanti |
fi |
| ethesis.language |
English |
en |
| ethesis.language |
engelska |
sv |
| ethesis.supervisor |
Mikko Airavaara |
und |
| ethesis.thesistype |
pro gradu -tutkielmat |
fi |
| ethesis.thesistype |
master's thesis |
en |
| ethesis.thesistype |
pro gradu-avhandlingar |
sv |
| ethesis.thesistype.URI |
http://data.hulib.helsinki.fi/id/thesistypes/mastersthesis |
|
| dct.identifier.ethesis |
E-thesisID:d1c2688b-3204-444b-994d-905975e8234f |
|
| ethesis-internal.timestamp.reviewStep |
2021-10-07 09:22:07:477 |
|
| dct.identifier.urn |
URN:NBN:fi:hulib-202111174035 |
|
| ethesis.discipline.med |
Neuroscience |
und |
| ethesis.facultystudyline |
Cross-disciplinary translational medicine |
fi |
| ethesis.facultystudyline |
Cross-disciplinary translational medicine |
en |
| ethesis.facultystudyline |
Cross-disciplinary translational medicine |
sv |
| ethesis.facultystudyline.URI |
http://data.hulib.helsinki.fi/id/SH_TMED-510 |
|
| ethesis.mastersdegreeprogram |
Translationaalisen lääketieteen maisteriohjelma (Translational Medicine) |
fi |
| ethesis.mastersdegreeprogram |
Master's Programme in Translational Medicine |
en |
| ethesis.mastersdegreeprogram |
Magisterprogrammet i translationell medicin |
sv |
| ethesis.mastersdegreeprogram.URI |
http://data.hulib.helsinki.fi/id/MH30_002 |
|
