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Neurosciences

Neurodegeneration

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Full-Text Articles in Medicine and Health Sciences

Protein Misfolding Toxicity And Inclusion Formation In Cellular Models Of Neurodegeneration, Sonja E. Di Gregorio Apr 2021

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 Role Of The Tau N-Terminal Phosphatase-Activating Domain And Phosphorylation At Thr175 In The Formation Of Tau Cytoplasmic Inclusions, Matthew A. Hintermayer Jul 2019

The Role Of The Tau N-Terminal Phosphatase-Activating Domain And Phosphorylation At Thr175 In The Formation Of Tau Cytoplasmic Inclusions, Matthew A. Hintermayer

Electronic Thesis and Dissertation Repository

Cytoplasmic inclusions and fibrils of the microtubule-associated protein tau (tau protein) are a key neuropathological hallmark in tauopathies, including Alzheimer’s disease, chronic traumatic encephalopathy, and amyotrophic lateral sclerosis with cognitive impairment. Previous research has demonstrated that the phosphorylation of tau protein at Thr175 is sufficient for the initiation of fibril formation both in vitro and in vivo. Here we use mutated tau protein constructs to demonstrate that phosphorylation at Thr175 results in the aberrant exposure of an N-terminal phosphatase-activating domain (PAD). The tau PAD interacts with protein phosphatase 1 (PP1) leading to the activation of glycogen synthase …


Examining The Role Of Ganglioside Homeostasis In Neurodegeneration And Aging Using Maldi Imaging Mass Spectrometry, Sarah Caughlin Feb 2018

Examining The Role Of Ganglioside Homeostasis In Neurodegeneration And Aging Using Maldi Imaging Mass Spectrometry, Sarah Caughlin

Electronic Thesis and Dissertation Repository

Gangliosides are a family of membrane lipids enriched in the central nervous system (CNS) that play an important role in cell signaling processes on the membrane. Alterations in the homeostatic distribution of the a-series family of gangliosides has been observed in both pre-clinical models and human patients with neurodegenerative diseases and injuries, such as Alzheimer’s disease (AD) and strokes. Ganglioside dysregulation has been implicated as an important mechanisms driving pathology in the aging brain, yet there is little information on where and when these lipid changes occur as well as the role of dysregulation during neurodegeneration. Matrix-Assisted Laser Desorption/Ionization (MALDI) …


Analyzing A-Series Gangliosides In Neurons Following Exposure To Glutamate, Dae Hee Park Aug 2015

Analyzing A-Series Gangliosides In Neurons Following Exposure To Glutamate, Dae Hee Park

Electronic Thesis and Dissertation Repository

Neurons within different brain regions have varying levels of vulnerability to external stress and therefore respond differently to injury. A potential reason to explain this may lie within a key lipid class of the cell’s plasma membrane called gangliosides. These glycosphingolipid species have been shown to play various roles in the maintenance of neuronal viability. The purpose of this study is to use electrospray ionization mass spectrometry (ESI-MS) technique and immunohistochemistry to evaluate the temporal changes in the expression profiles of various ganglioside species during the course of neurodegeneration in rat primary cortical neurons exposed to glutamate toxicity. Primary embryonic …


Mechanisms Of Atf4-Mediated Neuronal Apoptosis, Patrick Swan Apr 2015

Mechanisms Of Atf4-Mediated Neuronal Apoptosis, Patrick Swan

Electronic Thesis and Dissertation Repository

Abstract to be provided