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Thesis
Neuroprotective Role for Epigenetic Regulator Tip60 in Multiple Neurological Disorders
Master of Science (M.S.), Drexel University
May 2017
DOI:
https://doi.org/10.17918/etd-7351
Abstract
The advancing field of epigenetics focuses on the changes in phenotypes based on alterations in the chromatin structure rather than DNA mutations. Neurodegenerative diseases are of particular interest due to the devastating effects on the mind and body of those afflicted. Histone modifications through histone acetyltransferases (HATs) and histone deacetylases (HDACs) are common epigenetic alterations that occur in an array of neurological disorders. Our laboratory previously demonstrated that the HAT Tip60 plays a neuroprotective role in multiple cognitive processes impaired in Alzheimer's disease. Intriguingly, studies in animal models and post mortem brain tissues show that Huntington's disease, Parkinson's disease, and amyotrophic lateral sclerosis (ALS) all have one thing in common and that is a reduction of histone acetylation levels in the brain. Based on these observations, the hypothesis tested is that increasing Tip60 levels will induce neuroprotection by restoring HAT/HDAC balance and neural gene expression profiles disrupted in each of these diseases. To test my hypothesis, I induced increased levels of Tip60 specifically in the learning and memory center of the fly brain (termed the mushroom body) in Drosophila that model Huntington's disease, Parkinson's disease or ALS. An array of behavioral assays such as larvae crawling and longevity assays were used to determine whether increased Tip60 restores neural circuitry and function. These results may lay the groundwork for broad understanding of a potential neuroprotective role for Tip60 HAT action in multiple neurological disorders.
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Details
- Title
- Neuroprotective Role for Epigenetic Regulator Tip60 in Multiple Neurological Disorders
- Creators
- Renee Elisha Snook - DU
- Contributors
- Felice Elefant (Advisor) - Drexel University (1970-)
- Awarding Institution
- Drexel University
- Degree Awarded
- Master of Science (M.S.)
- Publisher
- Drexel University; Philadelphia, Pennsylvania
- Number of pages
- ix, 82 pages
- Resource Type
- Thesis
- Language
- English
- Academic Unit
- Biology; College of Arts and Sciences; Drexel University
- Other Identifier
- 7351; 991014632231404721