Date of Award
1-1-2018
Document Type
Masters Thesis
Degree Name
M.S.
Organizational Unit
College of Natual Science and Mathematics, Chemistry and Biochemistry
First Advisor
Erich G. Chapman, Ph.D.
Keywords
Amyotrophic lateral sclerosis, Protein aggregation, TDP-43, TAR-DNA-binding protein
Abstract
Protein aggregation and inclusion body formation are hallmarks of neurodegenerative diseases such as Alzheimer's, Parkinson's, Huntington's, and amyotrophic lateral sclerosis (ALS). These neurodegenerative diseases share a common pathology in that all include accumulation of insoluble protein aggregates in the brain. TAR-DNA-binding protein (TDP-43) is the major component found in the pathological inclusions of two of these diseases, ALS and frontotemporal lobar degeneration with ubiquitin-positive inclusions (FTLD-U). This thesis focuses upon the biophysical basis for TDP-43 aggregation in S. cerevisiae. Current in vitro evidence indicates that TDP-43 is a natively dimeric protein and that binding to RNA inhibits aggregation. Corresponding genetic results in yeast in which specific components of the RNA-decay machinery have been knocked-out, indicate that the buildup of specific cellular RNAs is capable of counteracting TDP-43 aggregation and toxicity in vivo. This thesis provides evidence of separate pathologies of TDP-43 and TDP-43 mutants in S. Cerevisiae. This thesis also introduces preliminary data of the effect of in vitro synthesized RNA on TDP-43 toxicity.
Publication Statement
Copyright is held by the author. User is responsible for all copyright compliance.
Rights Holder
Martin Anthony Aguilar
Provenance
Received from ProQuest
File Format
application/pdf
Language
en
File Size
62 p.
Recommended Citation
Aguilar, Martin Anthony, "Relationship Between TDP-43 Toxicity and Aggregation in Saccharomyces Cerevisiae" (2018). Electronic Theses and Dissertations. 1557.
https://digitalcommons.du.edu/etd/1557
Copyright date
2018
Discipline
Biochemistry
Included in
Biochemistry, Biophysics, and Structural Biology Commons, Neuroscience and Neurobiology Commons