Browsing Hood College by Subject "Activating Transcription Factor 6"
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ItemINVESTIGATING THE ROLE OF ATF6 IN ER STRESS IN AN IN VITRO MODEL OF ALZHEIMER’S DISEASE(2019-04-16) Eken, Ondine; Jones, Georgette; Biomedical ScienceAlzheimer’s disease (AD) is a neurodegenerative disease that is characterized by the accumulation of tau and amyloid-beta protein in the brain, forming neurofibrillary tangles and amyloid plaques, respectively. The endoplasmic reticulum (ER) has many critical functions such as protein processing, protein quality control, and protein folding. The ER sensors RNA-dependent protein kinase-like ER kinase (PERK), activating transcription factor 6 (ATF6), and inositol-requiring enzyme 1 (IRE1) are able to recognize amyloid-beta, misfolded proteins and initiates the Unfolded Protein Response (UPR). UPR plays a role in recovering homeostasis or triggering apoptosis of irreversibly damaged cells. There have been numerous studies involving PERK and IRE1, but little is known about ATF6 and its involvement with AD. Therefore, to better understand ER stressor ATF6 in AD, suppression of ATF6 with shRNA (short hairpin RNA) in neuroblastoma cell line (SH-S5SY) treated with A will be investigated. First, basal levels of ER stress will be measured to confirm the cells are an appropriate cell culture model for AD. This will be followed by knock down (KD) of ATF6 by shRNA and confirmation. Lastly, rescue of ATF6 will be performed to confirm that ATF6 is the cause of the downstream affects after silencing. Overall, these findings can contribute to the study and understanding ER stress sensor ATF6 and how delivery of shRNAs can aid in the regression of amyloid-beta, leading closer to understanding the molecular mechanism of AD.