The metabolism of APP protein in lysosomal storage disorders

Posavec, Melanija (2009) The metabolism of APP protein in lysosomal storage disorders. Diploma thesis, Faculty of Science > Department of Biology.

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Abstract

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.

Item Type: Thesis (Diploma thesis)
Keywords: APP, beta-amyloid precursor protein, cholesterol, Niemann-Pick type C disease (NPC disease), Alzheimer's disease
Supervisor: Katušić Hećimović, Silva
Date: 2009
Number of Pages: 39
Subjects: NATURAL SCIENCES > Biology
Divisions: Faculty of Science > Department of Biology
Depositing User: Silvana Šehić
Date Deposited: 12 Sep 2014 09:47
Last Modified: 12 Sep 2014 09:47
URI: http://digre.pmf.unizg.hr/id/eprint/2733

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