Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/15517
Title: Mechanism of U18666A-mediated cell death in cultured neurons
Authors: KOH CHOR HUI, VIVIEN
Keywords: U18666A; Neuronal apoptosis; Primary cortical neurons; Cholesterol; Niemann-Pick disease type C; Alzheimer’s disease
Issue Date: 17-Aug-2006
Source: KOH CHOR HUI, VIVIEN (2006-08-17). Mechanism of U18666A-mediated cell death in cultured neurons. ScholarBank@NUS Repository.
Abstract: Recent studies suggest that cholesterol imbalance and failure of homeostasis in the brain may lead to the development of neurodegenerative disorders such as Niemann-Pick disease type C (NPC) and Alzheimera??s disease (AD). U18666A is the most well-known pharmacological agent which inhibits cholesterol transport and is commonly used to mimic the NPC phenotype in normal cultured cells. In the present study, U18666A treatment leads to apoptosis and accumulation of intracellular free cholesterol in primary cortical neurons. Both the caspase and calpain proteolytic systems are activated upon treatment. There is also an increase in various oxidative stress markers. In addition, U18666A treatment induces hyperphosphorylation of tau and accumulation of intracellular I?-amyloid, mechanistic features reminiscent of AD. The profile of differentially-expressed genes in U18666A-mediated neuronal apoptosis is further studied through microarray analysis. An overview of the proteome changes during U18666A treatment is also determined using proteomics analysis. Implications of the findings are discussed.
URI: http://scholarbank.nus.edu.sg/handle/10635/15517
Appears in Collections:Ph.D Theses (Open)

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