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Investigating the function of CLU in Alzheimer's Disease in in vitro and in vivo models

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thesis
posted on 2021-11-15, 15:53 authored by Vithal, Tanisha

Alzheimer’s disease (AD) is a neurodegenerative disease that is responsible for 50-80% of dementia cases and is characterised by lack of visuospatial perception, impairment of language and memory. One of the main physiological attributions towards this disease is the accumulation of large insoluble deposits of amyloid beta, a toxic peptide, which results in the generation of amyloid plaques found in between neurons in the brain. Currently no therapeutic treatments are available. Clusterin (CLU) is an apolipoprotein that when defective is the second highest genetic risk factor for AD. It has been strongly debated whether CLU counteracts or promotes AD pathology. With the roles of CLU including but not limited to acting as a chaperone for cholesterol transport and aiding autophagy functionality in cancer models, this thesis investigates these two specific functionalities by overexpressing CLU in an in vitro SH-SY5Y and in an in vivo AD model of Drosophila melanogaster (fruit fly). Conclusions from this study reveal that within D. melanogaster, CLU reduced Aβ42 levels and increased cholesterol effect through the blood brain barrier. Additionally, in human cells, CLU ameliorated the defective flux in autophagy. This thesis sheds light into how CLU plays a protective role within an Alzheimer’s disease mammalian system.

History

Copyright Date

2016-01-01

Date of Award

2016-01-01

Publisher

Te Herenga Waka—Victoria University of Wellington

Rights License

Author Retains Copyright

Degree Discipline

Biotechnology

Degree Grantor

Te Herenga Waka—Victoria University of Wellington

Degree Level

Masters

Degree Name

Master of Science

ANZSRC Type Of Activity code

970106 Expanding Knowledge in the Biological Sciences

Victoria University of Wellington Item Type

Awarded Research Masters Thesis

Language

en_NZ

Victoria University of Wellington School

School of Biological Sciences

Advisors

Munkacsi, Andrew