Modeling the Effects of Supercomplex Formation and Stress Response on Alzheimer’S Disease Progression

• Main Author: Shelton, Morgan Griffin
• Format: Others
• Language: English
• Published: W&M ScholarWorks 2019
• Subjects: Biochemistry
• Online Access: https://scholarworks.wm.edu/etd/1563899025; https://scholarworks.wm.edu/cgi/viewcontent.cgi?article=6814&context=etd

Alzheimer’s disease is a specific form of dementia characterized by the aggregation of Amyloid-β plaques and tau tangles. New research has found that the formation of these aggregates occurs after dysregulation of respiratory activity and the production of radical oxygen species. Proteomic data shows that these changes are also related to unique gene expression patterns. We investigate the impact of these findings on new therapeutic options via metabolic flux analysis of sirtuin stress response pathways and respiratory supercomplex formation. Our results indicate CRISPR Cas-based gene therapy focused on upregulating stable CIII expression, and protective changes in SIRT1 and AMPK expression are potential avenues for therapeutics. This work also highlights the importance of metabolic enzyme activity in maintaining proper respiratory activity.