Transport of APP protein in organelles of endocytic pathway in CHO NPC1-null cells

Lisica, Ana (2009) Transport of APP protein in organelles of endocytic pathway in CHO NPC1-null cells. Diploma thesis, Faculty of Science > Department of Biology.

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Abstract

Altered metabolism and increased formation of amyloid-β peptide (Aβ) is considered to be the key event in development of Alzheimer's disease (AD). Recent reports have shown that cholesterol levels modulate processing of amyloid-β precursor protein (APP) and formation of Aβ peptide. Cholesterol accumulation and increased levels of Aβ peptide have also been observed in Niemann-Pick type C disease (NPC), hereditary sphingolipid storage disorder, which has become an important model to study the role of cholesterol in the pathogenesis of AD. The goal of this work was to investigate whether cholesterol accumulation in NPC disease changes distribution of APP protein and presenilin 1 (PS1) within endocytic pathway. Using immunoconfocal microscopy, we observed altered localization of APP protein in early and recycling endosomes in CHO NPC1-/- compared to CHOwt cells. In addition, we detected altered staining of markers for early (EEA1) and recycling (transferrin receptor, TFR) endosomes in CHO NPC1-/- cells, which suggests their accumulation on the cell periphery. However, altered localization of PS1 was not observed in endocytic organelles. These results suggest that cholesterol may influence the onset of AD by regulating trafficking of APP protein within endocytic pathway, and that this redistribution od APP protein leads to increased synthesis of C99, and Aβ peptide in these organelles.

Item Type: Thesis (Diploma thesis)
Keywords: APP, beta-amyloid precursor protein, cholesterol, NPC disease, Niemann-Pick type C, Alzheimer's disease
Supervisor: Katušić Hećimović, Silva
Co-supervisor: Hranilović, Dubravka
Date: 2009
Number of Pages: 34
Subjects: NATURAL SCIENCES > Biology
Divisions: Faculty of Science > Department of Biology
Depositing User: Silvana Šehić
Date Deposited: 09 Sep 2014 08:52
Last Modified: 16 Feb 2016 14:00
URI: http://digre.pmf.unizg.hr/id/eprint/2664

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