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Thesis_Md Moydul Islam.pdf (26.83 MB)

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Characterization of the Effect of Optineurin on Alpha-synuclein Aggregation and Toxicity in Yeast

Islam, Md Moydul
http://rave.ohiolink.edu/etdc/view?acc_num=wright1535409230684852

Abstract Details

2018, Master of Science (MS), Wright State University, Biological Sciences.
Optineurin, an autophagy adaptor protein genetically linked to Normal Tension Glaucoma and Amyotrophic Lateral Sclerosis, has been found in the pathological inclusions of various other neurodegenerative disorders, supporting an important role of optineurin in neurodegeneration. Using yeast as a model, we found that overexpression of optineurin drastically enhances the toxicity of the Parkinson's disease-causing protein, alpha-synuclein. Considering the conserved protein-protein interaction between optineurin and Ypt1, a yeast suppressor of the toxicity of both optineurin and alpha-synuclein, we hypothesize that cellular targets of optineurin underlie in the cytotoxicity and the enhancer effect. Using genome-wide yeast two-hybrid screens, we identified 97 yeast interacting proteins of optineurin and systematically tested their modifier effect on the toxicity of optineurin and alpha-synuclein. Given the neuroprotective effect of the mammalian homologs of Ypt1, the convergent pathways of the identified modifiers may represent conserved cellular perturbations induced by optineurin overexpression in higher eukaryotes.
Quan Zhong, Ph.D. (Advisor)
Mill Miller, Ph.D. (Committee Member)
Paula Bubulya, Ph.D. (Committee Member)
148 p.
Cellular Biology; Genetics; Neurosciences
Neurodegeneration; Optineurin; Alpha-synuclein; Amyotrophic Lateral Sclerosis; Normal Tension Glaucoma; Autophagy; Yeast model; Physical interaction mapping; Genetic interaction mapping

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Citations

  • Islam, M. M. (2018). Characterization of the Effect of Optineurin on Alpha-synuclein Aggregation and Toxicity in Yeast [Master's thesis, Wright State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=wright1535409230684852

    APA Style (7th edition)

  • Islam, Md Moydul. Characterization of the Effect of Optineurin on Alpha-synuclein Aggregation and Toxicity in Yeast. 2018. Wright State University, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=wright1535409230684852.

    MLA Style (8th edition)

  • Islam, Md Moydul. "Characterization of the Effect of Optineurin on Alpha-synuclein Aggregation and Toxicity in Yeast." Master's thesis, Wright State University, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=wright1535409230684852

    Chicago Manual of Style (17th edition)

wright1535409230684852
66
© 2018, all rights reserved.
This open access ETD is published by Wright State University and OhioLINK.