29th Annual Student Research Conference
Small Molecule ER Proteostatis Regulator Effects in SH-SY5Y Cells
L. Sofia Gonzalez
Dr. R. Luke Wiseman (Scripps Research Institute ), Dr. Christina Cooley (Trinity University ), and Dr. Laura Fielden, Faculty Mentors
The endoplasmic reticulum Secretory proteostasis network, made up in part by the unfolded protein response (UPR) allows cell response to disturbances in the proteostasis. Such disturbances include protein misfolding, protein over-secretion and protein under-secretion. Previous work done isolated small molecule activators that selectively upregulate the ATF6 arm of the UPR, which has shown to reduce protein secretion in pathologic models such as TTR25 protein and Amylogenic Light Chain (ALLC) secretion in hepatic cells without causing apoptosis. Research presented here aimed to explore a potential small molecule activator response to APP protein secretion, in particular he APP A subunit which heavily linked to the Alzheimer phenotype. SH-SY5Y cells were transfected to express both APPwt and APPswedish (Alzheimer disease related mutant). Preliminary results show the small molecules may reduce APP processing to smaller potentially amyloidogenic APPSwed cleavage products. These results open the possibility of the small molecules as tools for pharmacological study in Alzheimer?s treatment and research.
Keywords: Unfolded Protein Response , APP, Alzheimer Disease, ATF6 Activation
Topic(s):Biology
Chemistry
Presentation Type: Oral Paper
Session: -4
Location: MG 2001
Time: 10:15