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Thesis
Neuroprotective Effects of Pharmacological Exercise Mimetic Preconditioning on MPP+ -induced Neurotoxicity in Neuronal Cells
University of West Florida Libraries
Master of Science (MS), University of West Florida
2026
Abstract
Parkinson’s disease (PD) is characterized by the loss of dopaminergic neurons, with mitochondrial dysfunction and autophagic failure serving as key pathogenic mechanisms. This study investigated whether preconditioning with pharmacological exercise mimetic, 5-Aminoimidazole-4-carboxamide ribonucleoside (AICAR), known as an activator of adenosine monophosphate (AMP)-activated protein kinase (AMPK), could prevent 1-methyl-4-phenylpyridinium (MPP+)-induced neurotoxicity in dopaminergic neurons differentiated from SH-SY5Y cells. SH-SY5Y cells were differentiated into dopaminergic neurons using 10 μM retinoic acid for 7 days. To mimic exercise-induced cellular effects, cells were treated with 1 mM AICAR for 24 hours prior to exposure to 1 mM MPP+. The AICAR-dependent autophagy was confirmed using the autophagy inhibitor 3-methyladenine (3-MA). Western blot for protein expression, JC-1 staining for mitochondrial potential, and immunofluorescence for cell viability and microtubule-associated protein 1 light chain 3 (LC3) puncta assessment were used. AICAR rapidly activated the AMPK/ULK1 signaling axis within 1-2 hours, leading to increased LC3-II conversion and autophagosome formation. MPP+ exposure caused severe blockade of autophagic flux, loss of mitochondrial membrane potential, and oxidative damage, leading to apoptosis, while AICAR pretreatment restored autophagic flux, improved mitochondrial membrane potential and dynamics, and enhanced antioxidant capacity via heme oxygenase-1 induction, thereby suppressing apoptosis. Surprisingly, the protective benefits of AICAR were completely abolished when autophagy was inhibited by 3-MA; these findings demonstrate that AICAR-mediated autophagy restoration and mitochondrial quality control are essential for neuroprotection. This study provides mechanistic insight that pharmacological exercise mimetics can serve as a viable preventive strategy against PD progression.
Details
- Title
- Neuroprotective Effects of Pharmacological Exercise Mimetic Preconditioning on MPP+ -induced Neurotoxicity in Neuronal Cells
- Resource Type
- Thesis
- Contributors
- Youngil Lee (Committee Chair)Ludmila Cosio Lima (Committee Chair)Amy Crawley (Committee Chair)
- Publisher
- University of West Florida Libraries
- Format
- pdf
- Number of pages
- 90
- Copyright
- Permission granted to the University of West Florida Libraries by the author to digitize and/or display this information for non-profit research and educational purposes. Any reuse of this item in excess of fair use or other copyright exemptions requires the permission of the copyright holder.
- Identifiers
- 99381761652106600
- Academic Unit
- Usha Kundu, MD College of Health; Movement Sciences and Health
- Language
- English
- Awarding Institution
- University of West Florida; Master of Science (MS)
- Theses and Dissertations
- Master of Science (MS), University of West Florida