prikaz prve stranice dokumenta Molekularni učinci proteina alfa sinukleina u jezgri: vezanje na molekulu DNA i regulacija transkripcije
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doctoral thesis
Molekularni učinci proteina alfa sinukleina u jezgri: vezanje na molekulu DNA i regulacija transkripcije
Zagreb: University of Zagreb, Faculty of Science, 2014. urn:nbn:hr:217:426794
Gotovac, Kristina
University of Zagreb
Faculty of Science
Department of Biology

Institutional repository: Repository of the Faculty of Science

Cite this document

Gotovac, K. (2014). Molekularni učinci proteina alfa sinukleina u jezgri: vezanje na molekulu DNA i regulacija transkripcije (Doctoral thesis). Zagreb: University of Zagreb, Faculty of Science. Retrieved from https://urn.nsk.hr/urn:nbn:hr:217:426794

Gotovac, Kristina. "Molekularni učinci proteina alfa sinukleina u jezgri: vezanje na molekulu DNA i regulacija transkripcije." Doctoral thesis, University of Zagreb, Faculty of Science, 2014. https://urn.nsk.hr/urn:nbn:hr:217:426794

Gotovac, Kristina. "Molekularni učinci proteina alfa sinukleina u jezgri: vezanje na molekulu DNA i regulacija transkripcije." Doctoral thesis, University of Zagreb, Faculty of Science, 2014. https://urn.nsk.hr/urn:nbn:hr:217:426794

Gotovac, K. (2014). 'Molekularni učinci proteina alfa sinukleina u jezgri: vezanje na molekulu DNA i regulacija transkripcije', Doctoral thesis, University of Zagreb, Faculty of Science, accessed 22 November 2024, https://urn.nsk.hr/urn:nbn:hr:217:426794

Gotovac K. Molekularni učinci proteina alfa sinukleina u jezgri: vezanje na molekulu DNA i regulacija transkripcije [Doctoral thesis]. Zagreb: University of Zagreb, Faculty of Science; 2014 [cited 2024 November 22] Available at: https://urn.nsk.hr/urn:nbn:hr:217:426794

K. Gotovac, "Molekularni učinci proteina alfa sinukleina u jezgri: vezanje na molekulu DNA i regulacija transkripcije", Doctoral thesis, University of Zagreb, Faculty of Science, Zagreb, 2014. Available at: https://urn.nsk.hr/urn:nbn:hr:217:426794

Metadata
TitleMolekularni učinci proteina alfa sinukleina u jezgri: vezanje na molekulu DNA i regulacija transkripcije
Title (english)Molecular effects of protein alpha synuclein in the nucleus: DNA binding and transcriptional regulation
AuthorKristina Gotovac
MentorFran Borovečki (mentor)
MBZ: 230266
Committee memberVlatka Zoldoš (član povjerenstva)
Committee memberSanja Kapitanović (član povjerenstva)
Committee memberNevenka Meštrović Radan (član povjerenstva)
GranterUniversity of Zagreb
Faculty of Science
(Department of Biology)
Zagreb
Defense date and country2014, Croatia
Scientific / art field,
discipline and subdiscipline		NATURAL SCIENCES
Biology
Universal decimal classification
(UDC)		577 - Biochemistry. Molecular biology. Biophysics
Abstract
Protein alfa sinuklein uključen je u vezikularni transport u sinapsama neurona i regulaciju otpuštanja dopamina, te se smatra da igra važnu ulogu u nastanku Parkinsonove bolesti (PB). Točan mehanizam kojim ovaj protein utječe na oštećenje dopaminergičkih neurona, glavnog patološkog obilježja PB, još uvijek je nepoznat. Budući da je alfa sinuklein lokaliziran u jezgri neurona, te je pokazano da se vezuje za DNA, jedan od mogućih mehanizama jest deregulacija transkripcije. Glavni cilj predloženog istraživanja bio je istražiti učinak alfa sinukleina u jezgri, kao i moguće mehanizme deregulacije transkripcije na razini cijelog genoma u modelima PB. Analiza genske ontologije i signalnih putova pokazala je da su geni regrutirani od strane endogenog alfa sinukleina uključeni u organizaciju i funkcioniranje sinapse, kao i razvoj središnjeg živčanog sustava, te ubikvitinsko-proteasomski sustav. U stanicama koje eksprimiraju povećane količine alfa sinukleina od regrutiranih gena najviše su bili zastupljeni oni vezani uz regulaciju transkripcije, dok su u stanicama transfeciranim s mutiranim oblikom alfa sinukleina (A53T) regrutirani geni bili povezani s regulacijom apoptoze, ali i putovima uključenim u nastanak genetskih i neuroloških bolesti. Eksperimenti su pokazali značajan utjecaj endogenog i mutiranog alfa sinukleina na promotore gena NEDD4 (ubikvitin-ligaza), SLC4A5 (natrij bikarbonat kotransporter), NRXN3 (receptor i adhezijska molekula), ADRA1A (simpatički receptor) i MAP4K4 (mitogen aktivirana protein kinaza). Rezultati dobiveni provedenim istraživanjima ukazuju na potencijalni učinak alfa-sinukleina u jezgri, prije svega kroz utjecaj na mehanizme transkripcije, što u konačnici može doprinijeti razvoju PB.
Abstract (english)
Protein alpha synuclein is involved in vesicular transport on synapses and regulation of dopamine release. There is the evidence that alpha-synuclein may play an important role in in Parkinson`s disease (PD) development but the mechanism by which alpha synuclein damages dopaminergic neurons remains elusive. As alpha synuclein is located in the nucleus of neurons and it has been shown that it binds DNA, one of the possible mechanisms is transcriptional dysregulation. The aim of the project was to investigate possible effects of alpha-synuclein in the nucleus as well as possible mechanisms of transcriptional deregulation in PD models. Gene ontology analysis and pathways analysis showed that genes recruited by endogenous alpha synuclein are mostly involved in synapse functioning and organization, development of central nervous system and ubiquitin proteasome system. In cells overexpressing alpha synuclein most of the genes were related to nucleus and transcriptional regulation, while in cells transfected with mutated alpha synuclein (A53T) recruited genes were mostly involved in apoptosis regulation and pathways involved in development of genetic and neurologic diseases. Experiments showed significant influence of endogenous and mutated alpha synuclein on promoters of genes NEDD4 (ubiquitin-ligase), SLC4A5 (sodium bicarbonate cotransporter), NRXN3 (receptor and cell adhesion molecule), ADRA1A (adrenergic receptor) and MAP4K4 (mitogen activated protein kinase). Overall results show potential effect of alpha synuclein in the nucleus, primarily through effect on transcriptional mechanisms that can finally lead to Parkinson`s disease development.
Keywords
Keywords (english)
Languagecroatian
URN:NBNurn:nbn:hr:217:426794
Study programmeTitle: Biology
Study programme type: university
Study level: postgraduate
Academic / professional title: doktor/doktorica znanosti, područje prirodnih znanosti, polje biologija (doktor/doktorica znanosti, područje prirodnih znanosti, polje biologija)
Type of resourceText
File originBorn digital
Access conditionsClosed access
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Created on2017-05-17 12:57:02