Prion-like aggregation of Cu, Zn superoxide dismutase in amyotrophic lateral sclerosis.

Abstract

Neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis (ALS) are characterized by the aggregation of proteins and resulting neuronal death. Approximately 2% of all cases of ALS are caused by mutations to Cu, Zn Superoxide dismutase (SOD1). In Chapter One, I investigate the kinetics of generational prion-like seeding of SOD1 aggregation via thioflavin T fluorescence assays to better understand the utility of in vitro microplate- based assays for studying the inter-cellular transmission of SOD1 aggregates. Additionally, the relevance of the air-water interface and dependance on the concentration of the so-called “seed” are investigated. In Chapter Two, I selectively supercharge fibrils of SOD1 using derivates of FDA-approved PET agents for imaging amyloid in the brain. Using these compounds, I increased the net negative charge of fibrils of SOD1 (consisting of 103 subunits) by ~8,100 units. Chapter Three is dedicated to a project that aims to improve the accessibility of STEM education for blind and visually impaired students by 3D printing miniature models of globular proteins that can be visualized with the mouth.

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Keywords

Neurodegeneration. Protein aggregation. Lysine acetylation.

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