| |
| author |
Alyssa Baron
| | title |
Investigating the Role of mTOR Inhibition in Neurodegeneration: Rapamycin's Impact on an Alzheimer's Disease Model System
| | abstract |
Alzheimer's Disease (AD) is a progressive neurodegenerative disorder characterized by
cognitive decline, neuronal loss, and hallmark pathological features, such as amyloid-beta
plaques and neurofibrillary tangles (Scheltens et al., 2021). However, despite extensive efforts in
disease research, AD remains without a cure, with current treatments either merely relieving
symptoms rather than disease modification or fall short in efficacy, suggesting more to uncover
about the AD pathogenesis (Malik, 2017; Chhabra et al., 2024). The mammalian target of
rapamycin (mTOR) pathway plays a central role in cellular metabolism, protein synthesis, and
autophagy, and its dysregulation has been implicated in AD pathogenesis, particularly in its
inhibitory effects on neuronal autophagy and clearance of toxic protein aggregates (Laplante et
al., 2012; Cai et al., 2015). The goal of this study was to investigate the neuroprotective potential
of the drug rapamycin, an mTOR inhibitor, in mitigating oxidative stress-induced neurotoxicity
within an in vitro cell culture AD model system. Primary cortical neurons were exposed to
AD-like stressor conditions through Ferrous-Amyloid-Buthionine (FAB) exposure, to generate
oxidative stress similar to the AD mechanism. Assessment of rapamycin's therapeutic effects
was done through comparing quantified reactive oxidative stress produced and cell viability.
MitoSOX Red assays quantified reactive oxidative stress levels, while MTS assays measured
neuronal survival under various treatment conditions. Existing research has demonstrated that
oxidative stress plays a crucial role in AD pathology, and targeting reactive oxygen species
provide therapeutic benefit and neuroprotection (Tamagno, 2012). The findings suggest no
definitive results, due to limited data, but offer interesting trends suggesting rapamycin
pretreatment can reduce oxidative stress in combination with a stressor, supporting its potential
role in counteracting AD-related neurodegeneration. The trends seen align with previous studies
demonstrating rapamycin's ability to enhance cell autophagy clearance and reduce
neuroinflammation (Meijer et al., 2015). Future research, more trials, and comparison to cell
viability and neuronal morphology is necessary to confirm precise molecular mechanisms and
effects underlying rapamycin's application to an AD model system and, in turn, its efficacy as a
treatment.
| | school |
The College of Liberal Arts, Drew University
| | degree |
B.S. (2025)
|
| advisor |
Roger Knowles
|
| committee |
Christopher Fazen
Caitlin Killian
|
| full text | ABaron.pdf |
| |
