Monitoring transcriptomic responses of SH-SY5Y cells to amyloid treatments
Date
2013
Authors
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Publisher
University of Delaware
Abstract
Huntington’s disease is a progressive, fatal, autosomal dominant genetic disorder caused by an extension of CAG repeats in the Huntingtin (Htt) gene. Mutant Htt has an expanded poly-Q tract that results in a gain-of toxic function and formation of amyloid . Currently, there are no treatments available for slowing or preventing the disease progression and therefore, understanding the disease pathogenesis will aid in identifying therapeutic targets and treatments. Like Prions, mutant Htt inclusions have been hypothesized to cause native Htt to misfold and form amyloids. Here, using SH-SY5Y cells, mHtt amyloids and transcriptomic tools, we want to explore early events in the disease progression and identify preventative therapeutic targets (HD can be screened in pre-symptomatic patients). We observed that the mHtt amyloids did not induce significant differentially expressed genes (DEGs) in SH-SY5Y cells after amyloid treatment. But, DEGs based on t-tests affected calcium homeostasis and mitochondrial dysfunction mediated by PPARa. Overall, this thesis provides evidence to various hypotheses relating to mitochondrial dysfunction in HD pathogenesis. Further investigation of the transcriptome response by quantitative real time PCR will aid in understanding the causality between the DEGs and identify the hypothesis that best describes the transcriptome response.