Efects of TO901317 on APP processing in a cellular model of Niemann Pick type C disease

Živković, Jelena (2011) Efects of TO901317 on APP processing in a cellular model of Niemann Pick type C disease. Diploma thesis, Faculty of Science > Department of Biology.

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Abstract

It is known that cholesterol and its accumulation is associated with the development of Alzheimer's disease. Liver X receptors (LXR) act as cholesterol sensors and modify the expression of genes involved in its transport, catabolism and elimination, which makes them a potential, new targets in the study of the relationship of cholesterol and Alzheimer's disease. Today, more and more researches are examining synthetic LXR receptor ligands, and one of the most studied is TO901317. The aim of this study was to investigate the effects of synthetic LXR ligand receptor (TO901317) on the processing of APP protein in the cell model of NPC disease. Experiments were conducted on the parental wild-type cells (CHOwt )and on the cells with stably deleated NPC1 gene (CHO-NPC1-/ -) . The results show that treatment of cells with TO901317 induced activation of LXR receptors, which led to increased transcription of genes that encode transmembrane transporters of cholesterol. Also, it appeares that TO901317 has an impact on the processing of APP protein, on the endogenous and exogenous levels and causes a trend of increasing or decreasing levels of certain proteins. These results indicate that the treatmen with synthetic ligand TO901317 does have an effect on the treated cells, and also suggest that these therapies could lead to an increase of α-secretase activity and thus lower the β-secretase activitiy, which could possibly prevent the accumulation of Aβ peptide.

Item Type: Thesis (Diploma thesis)
Keywords: amyloid precursor protein (APP), amyloid- β, cholesterol , liver X receptors (LXR), Alzheimer's disease, Niemann-Pick type C disease
Supervisor: Štefulj, Jasminka
Co-supervisor: Oršolić, Nada
Date: 2011
Number of Pages: 46
Subjects: NATURAL SCIENCES > Biology
Divisions: Faculty of Science > Department of Biology
Depositing User: Grozdana Sirotic
Date Deposited: 10 Jul 2014 11:48
Last Modified: 18 Sep 2014 11:56
URI: http://digre.pmf.unizg.hr/id/eprint/2488

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