Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/16361
Title: The role of cholesterol sequestration and accumulation in the endocytic pathway in development of neurodegenerative diseases
Authors: HUANG ZHILI
Keywords: Cholesterol, Apoptosis, Neurodegenerative, Embryonic, Cortex, Neuron.
Issue Date: 10-Jul-2009
Source: HUANG ZHILI (2009-07-10). The role of cholesterol sequestration and accumulation in the endocytic pathway in development of neurodegenerative diseases. ScholarBank@NUS Repository.
Abstract: Niemann-Pick type C (NPC) disease is characterized by accumulation and sequestration of unesterified cholesterol in the endocytic pathway and progressive neurodegeneration. The cellular mechanism of NPC phenotype is still under investigation. In this study, I demonstrate inhibition of intracellular cholesterol trafficking in primary neurons by class 2 amphiphiles, which mimics the major biochemical and cellular feature of NPC1, led to not only impaired mitochondrial function but also activation of the mitochondrial apoptosis pathway. cAMP has been shown to improve the survival in vitro of several neuronal types when added to the medium. In this study, I demonstrate that significant upregulation of Rab7 expression and mild increase of rab9 expression with treatment of cAMP and forskolin to primary neurons and NPC1 fibroblasts, through activation of ERK, leading to survival of cells. In this process, cholesterol trafficking is modulated, and cholesteryl ester is increased in both types of cells.
URI: http://scholarbank.nus.edu.sg/handle/10635/16361
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