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Milliken Mercer Dissertation.pdf (1.86 MB)

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The Role of ADAR editing in Parkinson's Disease

Mercer, Heather Milliken
http://rave.ohiolink.edu/etdc/view?acc_num=kent1721308586463335

Abstract Details

2024, PHD, Kent State University, College of Arts and Sciences / Department of Biological Sciences.
Parkinson’s Disease (PD) is a multifactorial disease with heterogenous phenotypes that vary across individuals, as well as by age and sex. Therefore, it is likely that multiple interacting factors, such as environmental influences and aging, as well as genetic factors, including dynamic RNA editing, via ADARs (Adenosine Deaminases Acting on RNA), may play a role in PD pathology. Here we explored changes in ADAR editing in PD in two datasets: one consisting of skeletal muscle transcriptomes from a small cohort of male PD patients and controls, including those that engaged in a rehabilitative exercise training program, and a second dataset of 317 transcriptomes of healthy controls, PD and prodromal patients aged 65 years or older, from the Parkinson’s Project Markers Initiative dataset. We observed differences in ADAR expression, number of putative ADAR edits, editing index, and the number of high and moderate impact edits between control groups and diseased samples, between sexes, and between PD samples pre- and post-exercise, particularly when ADAR editing is associated with nonsense-mediated decay (NMD). Likewise, differentially expressed genes between comparison groups were linked to NMD-related pathways. NMD is an important process in detecting deleterious nonsense sequences in mRNA transcripts and eliminating them from the cell. Thus, NMD regulation serves an important role in neurodevelopment, neural differentiation, and neural maturation. RNA misprocessing, which includes dysregulation of NMD, is known to play an important role in neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and fronto-temporal dementia. Our results suggest that NMD may also be an important factor in PD physiology.
Helen Piontkivska, Ph.D. (Advisor)
170 p.
Bioinformatics; Biology; Genetics

Recommended Citations

Citations

  • Mercer, H. M. (2024). The Role of ADAR editing in Parkinson's Disease [Doctoral dissertation, Kent State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=kent1721308586463335

    APA Style (7th edition)

  • Mercer, Heather. The Role of ADAR editing in Parkinson's Disease . 2024. Kent State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=kent1721308586463335.

    MLA Style (8th edition)

  • Mercer, Heather. "The Role of ADAR editing in Parkinson's Disease ." Doctoral dissertation, Kent State University, 2024. http://rave.ohiolink.edu/etdc/view?acc_num=kent1721308586463335

    Chicago Manual of Style (17th edition)

kent1721308586463335
56
© 2024, all rights reserved.
This open access ETD is published by Kent State University and OhioLINK.