Evaluating suspected CWD feral pig brain samples using RT-QuIC and protocol for the purification and quality control of recombinant monomeric proteins for RT-QuIC assay

<p>Proteinopathy is a broad term used to describe any disease or condition that arises as</p> <p>a result of aberrant protein behavior. Most often it is used when discussing any of a wide</p> <p>range of neurodegenerative diseases that tend to result from an abnormal misfolding and</p> <p>subsequent aggregation of a normal cellular protein. The pathology of each of these diseases</p> <p>is largely dependent upon the nature of the protein aggregate that is responsible for or</p> <p>resulting from the disease. When viewed individually each disease seems only vaguely</p> <p>similar to others, but when a step back is taken to consider the broader aspects of the disease</p> <p>it begins to show similarities with other diseases, some of which are better studied and</p> <p>understood. The advances in other proteinopathies can then be experimentally applied to a</p> <p>specific disease of interest and the results compared to gain better understand the</p> <p>mechanisms underlying its pathogenesis and progression.</p> <p>Two examples of such proteinopathies are transmissible spongiform encephalopathies</p> <p>(TSE) and Parkinson’s disease (PD). TSEs are a subset of prion misfolding diseases,</p> <p>specifically identified as being transmissible to other individuals in a manner resembling</p> <p>viral, bacterial, or toxic exposure, that have been studied in animals for decades. While rare</p> <p>in humans, prion protein misfolding does occur in a handful of different forms. PD on the</p> <p>other hand is fairly common in older individuals, affecting approximately one million people</p> <p>in the United States and an estimated 10 million people worldwide. Both conditions share</p> <p>such notable traits as characteristic protein aggregates, being neurodegenerative, eventually</p> <p>fatally so, and having a link to the enteric nervous system. Techniques applied to the study of</p> <p>TSEs have been successfully applied to the study of PD, and inverse has occurred as well,</p> <p>leading to leap frog effect of advancement for both diseases.</p> <p>In this thesis, topics of two proteinopathies are covered. A literature review of chronic</p> <p>wasting disease (CWD) history, study, and further interests leads the paper. This is followed</p> <p>by a chapter on analysis of feral pig brainstem by RT-QuIC to determine the presence or</p> <p>absence of aggregated prion protein. The next chapter is dedicated to describing a protocol</p> <p>for the efficient and reliable production of recombinant human α-synuclein monomeric</p> <p>protein for use in research. Each of these techniques has been applied to the study of multiple</p> <p>diseases, but the refinement of each technique for application to the disease or species of</p> <p>interest is essential to achieving the best results.</p>

Name thesis:degree_name

Master of Science

Level thesis:degree_level

thesis

Discipline thesis:degree_discipline

Biomedical Sciences

Department dc:contributor.department

Department of Veterinary Microbiology and Preventive Medicine

Year dc:date.issued

2019

Author dc:creator

• Hepker, Monica

Advisor dc:contributor.advisor

• Anumantha Kanthasamy

Language dc:language.iso

en

Identifier

archive/lib.dr.iastate.edu/etd/17202/

OAI identifier oai:identifier

oai:dr.lib.iastate.edu:20.500.12876/31385