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master's thesis
Metabolizam proteina APP u lizosomskim bolestima nakupljanja
Zagreb: University of Zagreb, Faculty of Science, 2009. urn:nbn:hr:217:840841
Posavec, Melanija
University of Zagreb
Faculty of Science
Department of Biology

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Posavec, M. (2009). Metabolizam proteina APP u lizosomskim bolestima nakupljanja (Master's thesis). Zagreb: University of Zagreb, Faculty of Science. Retrieved from https://urn.nsk.hr/urn:nbn:hr:217:840841

Posavec, Melanija. "Metabolizam proteina APP u lizosomskim bolestima nakupljanja." Master's thesis, University of Zagreb, Faculty of Science, 2009. https://urn.nsk.hr/urn:nbn:hr:217:840841

Posavec, Melanija. "Metabolizam proteina APP u lizosomskim bolestima nakupljanja." Master's thesis, University of Zagreb, Faculty of Science, 2009. https://urn.nsk.hr/urn:nbn:hr:217:840841

Posavec, M. (2009). 'Metabolizam proteina APP u lizosomskim bolestima nakupljanja', Master's thesis, University of Zagreb, Faculty of Science, accessed 20 November 2024, https://urn.nsk.hr/urn:nbn:hr:217:840841

Posavec M. Metabolizam proteina APP u lizosomskim bolestima nakupljanja [Master's thesis]. Zagreb: University of Zagreb, Faculty of Science; 2009 [cited 2024 November 20] Available at: https://urn.nsk.hr/urn:nbn:hr:217:840841

M. Posavec, "Metabolizam proteina APP u lizosomskim bolestima nakupljanja", Master's thesis, University of Zagreb, Faculty of Science, Zagreb, 2009. Available at: https://urn.nsk.hr/urn:nbn:hr:217:840841

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Metadata
TitleMetabolizam proteina APP u lizosomskim bolestima nakupljanja
Title (english)The metabolism of APP protein in lysosomal storage disorders
AuthorMelanija Posavec
MentorSilva Katušić Hećimović (mentor)
Committee memberDubravka Hranilović (predsjednik povjerenstva)
Committee memberMirta Tkalec (član povjerenstva)
Committee memberMaja Matulić (član povjerenstva)
GranterUniversity of Zagreb
Faculty of Science
(Department of Biology)
Zagreb
Defense date and country2009, Croatia
Scientific / art field,
discipline and subdiscipline		NATURAL SCIENCES
Biology
Abstract
Nedavna istraživanja su pokazala da povišena razina kolesterola može mijenjati cijepanje prekursora proteina amiloid-beta (APP) i utjecati na nakupljanje peptida amiloid-beta (Aβ), glavne patološke značajke Alzheimerove bolesti (AB). Nakupljanje kolesterola u endosomima/lizosomima u bolesti Niemann-Pick tipa C (NPC) prati značajno povećanje razine peptida Aβ i C-terminalnog odsječka proteina APP - C99. Cilj rada je bio ispitati način djelovanja kolesterola na smještaj proteina APP i/ili presenilina 1 (PS1) u stanične organele u bolesti NPC. Uporabom modelnih stanica CHO NPC1-null i stanica divljeg tipa (CHOwt) u razdvajanju unutarstaničnih organela centrifugiranjem u gradijentu Iodixanola, utvrđeno je da stanice CHO NPC1-null pokazuju promijenjen smještaj proteina APP i PS1 te povišenu razinu kolesterola i odsječka C99 u ranim/kasnim endosomima. Ovi rezultati ukazuju da kolesterol najvjerojatnije doprinosi nastanku AB regulirajući smještaj proteina APP i PS1 unutar organela endocitoznog puta, središnjem mjestu stvaranja peptida Aβ u stanici, te da ova preraspodjela može dovesti do povećanog stvaranja peptida Aβ.
Abstract (english)
Recent reports have suggested that elevated cholesterol levels may modulate processing of beta-amyloid precursor protein (APP) by increasing formation of the amyloid-beta (Aβ) peptide, a central event in the pathogenesis of Alzheimer’s disease (AD). Cholesterol accumulation in endosomes/lysosomes in Niemann-Pick Type C (NPC) disease is accompanied by a significant increase in Aβ levels and levels of the Cterminal APP fragment – C99. The goal of this work was to investigate the cholesterol accumulation-regulated subcellular redistribution of APP and/or presenilin 1 (PS1) in NPC disease. To test this we utilized NPC model cells (CHO NPC1-null) and parental CHOwt cells. Using subcellular fractionation we observed altered subcellular localization of APP and PS1 together with increased C99 levels in early/late endosomes in CHO NPC1-null vs. CHOwt cells. Our findings suggest that cholesterol may contribute to AD onset by altering trafficking of APP and PS1 within endocytic pathway leading to increased formation of Aβ.
Keywords
Keywords (english)
Languagecroatian
URN:NBNurn:nbn:hr:217:840841
Study programmeTitle: Molecular Biology
Study programme type: university
Study level: graduate
Academic / professional title: magistar/magistra molekularne biologije (magistar/magistra molekularne biologije)
Type of resourceText
File originBorn digital
Access conditionsOpen access
Terms of useLicence In copyright icon
RepositoryRepository of the Faculty of Science
Created on2018-03-15 10:41:04

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