Investigating early cellular and molecular responses to misfolded protein

Abstract

PMDs such as AD, PD, HD and TSE are associated with the accumulation of abnormally folded proteins. However, the mechanisms involving seeding, processing and degradation of these rogue proteins are poorly understood. In this project, the response of primary hippocampal cultures to fibril challenge was investigated on a transcriptome level. This provided insights into molecular mechanisms associated with misfolded protein handling using cultures that either support misfolded protein generation (101LL) or that curtail its production (WT). Initial baseline transcriptome profiles were generated by microarray analysis then a more comprehensive analysis using RNA-sequencing (RNA-seq) for pre and post-fibril challenge transcriptome analysis was carried out.