Development of AD in C. Elegans by Inhibiting Combinations of SGK, AKT, and PDK1

Overview

Alzheimer's Disease (AD) is a neurodegenerative disease that impacts more than 6 million Americans of all ages (Alzheimer's Association, 2023). The etiology of AD is the accumulation of amyloid-beta plaques in the brain, driven by disruptions in insulin-signaling pathways. These pathways play a vital role in regulating cellular processes, including metabolism and synaptic plasticity. To gain a better understanding of Alzheimer's Disease and pave the way for effective interventions, the model organism Caenorhabditis Elegans (C. elegans) was utilized. C. elegans offer a powerful tool for studying AD and uncovering potential therapeutic targets due to its simple nervous system and shared fundamental biological processes with humans. This project investigates the intricate relationship between the insulin/IGF-1 signaling (IIS) pathway and AD progression, with a focus on three pivotal components: SGK-1, AKT, and PDK. These protein kinases are key regulators within the IIS pathway and have been implicated in crucial cellular processes related to AD, such as amyloid-beta production. By strategically inhibiting SGK-1, AKT, and PDK in C. elegans, this project will uncover the individual and combined effects on AD pathology. By using strains of C. elegans that have AD and share the IIS-pathway with humans, measuring paralysis progression and amyloid-beta protein production, will determine if inhibiting parts of the IIS-pathway in various combinations influence amyloid-beta production, and overall disease progression. By unraveling the complex interplay between insulin-signaling pathways and AD pathology in C. elegans, this project will identify novel therapeutic targets that are capable of revolutionizing Alzheimer’s Disease treatment strategies.