Life Sciences Commons^™

Antioxidant Biomarkers And Nutraceutical Therapeutics In Neurodegeneration And Neurotrauma, Lilia A. Koza

Electronic Theses and Dissertations

Mild traumatic brain injury (mTBI), yielding a Glascow Coma Scale of 13-15, is the most commonly occurring severity of TBI. Pathology from mTBI consists of blood brain barrier disruption, neuroinflammation, oxidative stress, excitotoxicity, mitochondrial dysfunction, protein aggregation, axonal degeneration, and resulting neuronal death. These processes deplete the body’s endogenous antioxidant system. We report a retrospective analysis of antioxidant blood biomarkers in patients with a history of mTBI from a local sports medicine clinic, Resilience Code. We found persistent sex-specific antioxidant depletions in mTBI patients associated with worsened symptomology.

Certain populations, such as athletes, are at high risk for repetitive mTBI …

Characterization Of A Phosphomimetic Mutant Of The Als Associated Protein Tdp-43, Nicole Toro

Electronic Theses and Dissertations

Trans-activation response (TAR) DNA-binding protein 43 (TDP-43) is a natively dimeric 414-residue protein that is encoded by the human TARDBP gene that has important implications in the pathogenesis of the neurodegenerative disorders ALS, FTD, and CTE. TDP-43 has been found hyperphosphorylated and ubiquitinated in the aggregates of the affected neurons of these diseases. The discovery of the presence of TDP-43 positive inclusions in brain matter of patients with CTE has made repetitive brain injury a possible environmental stimulus for aggregation in TDP-43 proteinopathies. We expand upon the hypothesis that TDP-43 readily aggregates under agitation conditions and that the addition of …

Relationship Between Tdp-43 Toxicity And Aggregation In Saccharomyces Cerevisiae, Martin Anthony Aguilar

Electronic Theses and Dissertations

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 …

The Neuroprotective And Therapeutic Effects Of Anthocyanins And Their Metabolites In Vitro And In A Mouse Model Of Amyotrophic Lateral Sclerosis, Aimee Nicole Winter

Electronic Theses and Dissertations

Anthocyanins, a unique class of flavonoid compounds, have recently come to the forefront of investigative research aimed at evaluating the potential applications of natural products to human health. Evidence demonstrating the beneficial effects of anthocyanin consumption has been reported for a myriad of conditions including cancer, cardiovascular disease, and lately, neurodegenerative disease. Neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis (ALS) are characterized by the death of specific neuronal populations within the brain and spinal cord, leading to cognitive and/or motor impairment. While the etiology of many of these diseases is largely unknown, several factors have …

Mitochondrial Glutathione Transport: Implications For Bcl-2 And Neuronal Survival, Heather Marie Wilkins

Electronic Theses and Dissertations

Oxidative stress is a contributing factor to many neurodegenerative diseases. In particular, mitochondria are a key source of oxidative stress due to electron leakage at the level of the electron transport chain. To combat the endogenous production of reactive oxygen and reactive nitrogen species mitochondria are equipped with several redox-cycling systems, such as glutathione (GSH). Mitochondrial GSH has been shown to be a critical reservoir of this antioxidant, where selective depletion of mitochondrial GSH can induce apoptosis in several systems. Many studies have intricately linked Bcl-2 to cellular GSH status and it has been previously shown that Bcl-2 is a …

Role Of Pro-Apoptotic Bcl2-Homology-3 Domain (Bh3)-Only Proteins In The Mutant Sod1 Mouse Model Of Als, Anna George Andrianakos

Electronic Theses and Dissertations

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease involving rapid degeneration of motor neurons in the spinal cord and retraction of their axonal projections to the neuromuscular junctions. Several known mutations linked to some familial cases of ALS have been linked to mutations in Cu/Zn superoxide dismutase (SOD1), resulting in mitochondrial oxidative stress and intrinsic apoptosis. Transgenic mice expressing a G93A mutant of SOD1 provide an in vivo model to investigate motor neuron death during disease progression. The principal regulators of intrinsic apoptosis are the Bcl-2 family proteins. While some members of this family are pro-survival, the Bcl-2 homology-3 …