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University of Denver

Neurodegenerative diseases

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Full-Text Articles in Biochemistry

Inhibition Of De Novo And The Prion-Like Spread Of Amyloidogenesis Using In Vitro And In Vivo Disease Models, Johnson Anazoba Joseph Jan 2022

Inhibition Of De Novo And The Prion-Like Spread Of Amyloidogenesis Using In Vitro And In Vivo Disease Models, Johnson Anazoba Joseph

Electronic Theses and Dissertations

The aberrant fibrous, extracellular, and intracellular proteinaceous deposits in cells, organs and tissues are referred to as amyloids. These deposits are dominated by β-sheet structures that have been implicated in several neurodegenerative diseases and cancer. In this work, the types of amyloidosis studied include Parkinson’s disease (PD) using UA196 and NL5901 strains of Caenorhabditis elegans (C. elegans), Alzheimer’s disease (AD) using GMC101 strain of C. elegans, and cancer-associated mutant p53 aggregation in MIA PaCa-2 mutant cells. Several molecules including SK-129, NS132, NS163, bexarotene, a polyphenol (-)-epi-gallocatechine gallate (EGCG), ADH40, RD148, and RD242 were screened in vitro and in …


Mechanistic Insight Into Tau Fibril Cross-Seeding Barriers: Structural Order And Disorder, Hilary Ann Weismiller Jan 2019

Mechanistic Insight Into Tau Fibril Cross-Seeding Barriers: Structural Order And Disorder, Hilary Ann Weismiller

Electronic Theses and Dissertations

Filamentous deposition of microtubule-associated protein tau is a hallmark for a number of neurodegenerative diseases collectively termed tauopathies. While tau fibrils are directly linked to the etiology and pathogenesis of these diseases, fibril morphology and their phenotypic presentation can be quite disparate. Alternative splicing of tau results in two main isoform groups, four-repeat (4R) tau and three-repeat (3R), identified by their number of microtubule binding repeats. Some diseases show deposition of both 4R and 3R isoforms, while others show preferential deposition of only one type. The conformational templated growth scheme and trans-synaptic spreading of fibrils is influenced by fibril conformation. …