Life Sciences Commons^™

Protein Misfolding Toxicity And Inclusion Formation In Cellular Models Of Neurodegeneration, Sonja E. Di Gregorio

Electronic Thesis and Dissertation Repository

Protein misfolding characterizes most neurodegenerative diseases. Protein misfolding is the conversion of specific proteins from their normal, often soluble, and native three-dimensional conformation into an aberrant, often insoluble, non-functional conformation. Protein inclusions and aggregates are among the major pathological hallmarks of protein misfolding associated with many neurodegenerative diseases. Yet, the role of aggregates and inclusions is not clearly defined and heavily debated. This study utilizes powerful genetic approaches in yeast and verification in mammalian neuronal cell lines to address the misfolding and toxicity of three proteins, the Rho Guanine Nucleotide Exchange Factor (RGNEF), Matrin3, which are involved in amyotrophic lateral …

The Leucine-Rich Domain Of Rgnef: A Modifier Of Tdp-43 Toxicity In Drosophila Melanogaster., Benjamin Martin Withers

Electronic Thesis and Dissertation Repository

Abstract

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the progressive degeneration of motor neurons. Rho Guanine Nucleotide Exchange factor (RGNEF) like other RNA-binding proteins, has been observed to form inclusions in the spinal cord motor neurons of both sporadic and familial cases of ALS. RGNEF has been determined to be a pro-survival factor under stress conditions. When comparing expression of different constructs of RGNEF in HEK293T cells, a Leucine-rich domain containing fragment of RGNEF (L-Rich) was found to form aggregates under metabolic stress that co-aggregated with TDP-43, another ALS-linked RNA-binding protein.

In this thesis, I used both …

The Role Of The Rna-Binding Protein Rho Guanine Nucleotide Exchange Factor In The Cellular Stress Response, Kevin Wh Cheung

Electronic Thesis and Dissertation Repository

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease for which the pathological mechanism is heterogeneous and a cure has been elusive. Recent developments have linked specific proteins found in pathological neuronal cytoplasmic inclusions (NCIs) of ALS motor neurons to familial variants of the disease. These proteins, including TAR DNA-binding protein of 43 kDa (TDP-43), fused in sarcoma/translocated in liposarcoma (FUS), and Rho guanine nucleotide exchange factor (RGNEF) share the common characteristic of being RNA-binding proteins that colocalize within NCIs. RGNEF is unique however in also possessing RhoA activation capacity, suggesting a role in the cell stress response. My thesis …