Theses
Date of Award
2025
Document Type
Thesis
Degree Name
Master of Science (MS)
Department
Biological Sciences
First Advisor
Dr. Derek Huffman
Second Advisor
Dr. Kristina Ames
Abstract
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, with neuroinflammation playing a central role in its pathophysiology. In this study, we investigated the effects of several pharmacological treatments Spermidine (SPERM), Rapamycin (RAPA), Metformin (MET), Lithium Carbonate (LI2CO3), and Fasudil (FASUDIL) on inflammation-related signaling pathways in the 5XFAD mouse model of AD. Previous research suggests that modulation of key inflammatory pathways, such as mTOR and NF-κB, could reduce neuroinflammation and potentially slow AD progression. However, the exact impact of these treatments on relevant pathways, particularly in peripheral tissues like the liver, remains unclear. We hypothesize that identifying gerotherapeutics that most effectively limit neuroinflammation will serve as effective single agents as well as in combination with other agents acting on distinct aging hallmarks to limit disease progression in 5XFAD mice. Our findings show that while treatments like SPERM and RAPA modestly modulate inflammatory markers in both brain and liver tissues, there were no significant alterations in key mTOR and NF-κB signaling pathways. This suggests that while systemic inflammation could impact central inflammation, the effects of these treatments on AD-related inflammatory pathways are limited. Furthermore, the liver-brain axis plays a key role in regulating systemic inflammation, suggesting that future therapies targeting both peripheral and central inflammation may be more effective in treating AD. These findings provide a foundation for future research exploring more targeted therapies that modulate inflammation in both brain and peripheral tissues, as well as personalized approaches based on patient-specific inflammatory profiles. This study highlights the complexity of targeting inflammation in AD and underscores the need for further investigation into long-term effects, combination therapies, and more specific molecular targets for therapeutic development.
Recommended Citation
Ciprian, Wilber R., "Identification of Gerotherapeutics that can effectively reduce neuroinflammation in Alzheimer Disease." (2025). CUNY Academic Works.
https://academicworks.cuny.edu/le_etds/45
