Subject Area

Cell Biology, Molecular Biology, Neuroscience

Abstract

Neurodegenerative diseases have a large negative impact to human society. Symptoms of neurodegenerative diseases includes memory loss, impaired recognition, motor dysfunction due to dysregulated neuronal loss in different brain regions. However, the neurobiological basis of these brain diseases is not fully understood and there are no cures or effective treatments. Polyglutamine (Poly-Q) disorders is a class of neurodegenerative diseases that are caused by polyglutamine expansion within the protein coding regions of specific genes. Huntington’s disease (HD), Spinal Cerebellar Ataxia Type 1 (SCA1) and Spinal Cerebellar Ataxia Type 3 (SCA3) are three common diseases among Poly-Q disorders. To better understand the neurobiology of these disorders and further to develop a potential treatment, I focused my dissertation research on p65 which was reported by our laboratory to prevent low-potassium (LK) condition induced program cell death in cerebellar granule neurons (CGN). I discovered that p65 was protective against toxicities in disease models of these disorders. p65 was also showed to prevent neuronal death under oxidative stress in cortical neurons. The protective effect of p65 depended on the Serine at aa276. Mutating p65 S276 to a non-phosphorylatable Alanine (S276A) abrogated the protection of p65 in models of Huntington’s disease and conditions of LK; however, mutating to phosphomimetic Aspartate (S276D) completely protected neurons.

Degree Date

Summer 8-2020

Document Type

Dissertation

Degree Name

Ph.D.

Department

Biological Sciences

Advisor

Dr. Jonathan E. Ploski

Second Advisor

Dr. William C. Orr

Third Advisor

Dr. Richard S. Jones

Fourth Advisor

Dr. Robert Harrod

Number of Pages

48

Format

.pdf

Creative Commons License

Creative Commons Attribution-Noncommercial 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial 4.0 License

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