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Thesis
Characterization of tabersonine derivatives as potential treatment for Alzheimer's disease in Drosophila melanogaster
Master of Science (M.S.), Drexel University
Jun 2020
DOI:
https://doi.org/10.17918/00001008
Abstract
Alzheimer's disease (AD) is a progressive neurodegenerative disease which has pathologies linked to accumulation of A[beta] plaques in the brain. Despite being prevalent on a global scale, there remains no cure and few treatments for the disease. A drug treatment which interferes with underlying causes of AD is badly needed. Here we explore the ability of tabersonine, an indole alkaloid, and several tabersonine derivatives to interfere with A[beta] deposition in our well-characterized Drosophila melanogaster model of AD. Our results suggest that while tabersonine shows some ability to improve motor function in our model, its derivatives can provide an even greater rescue effect. Screening of several derivative compounds led to the identification of a compound known as "Shelley" which appeared to have excellent anti-AD activity. Treatment with "Shelley" results not only in a rescue of motor defects in AD model organisms to levels undiscernible from healthy organisms, but also a significant decrease in the number of A[beta]-42 fragments detectable in the brain. Tabersonine and its derivatives show great promise in our model at being able to rescue biochemical and behavioral effects of AD by targeting underlying causes, and we suggest that they may prove to be therapeutically useful with further study and characterization.
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Details
- Title
- Characterization of tabersonine derivatives as potential treatment for Alzheimer's disease in Drosophila melanogaster
- Creators
- Carly J. Smith
- Contributors
- Daniel Marenda (Advisor)John Bethea (Advisor)
- Awarding Institution
- Drexel University
- Degree Awarded
- Master of Science (M.S.)
- Publisher
- Drexel University; Philadelphia, Pennsylvania
- Number of pages
- vii, 40 pages
- Resource Type
- Thesis
- Language
- English
- Academic Unit
- Biology; College of Arts and Sciences; Drexel University
- Other Identifier
- 991014695140804721