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Articles 1 - 11 of 11
Full-Text Articles in Biochemistry, Biophysics, and Structural Biology
Cyclophilin 40 As A Novel Disaggregase, Jeremy Dustin Baker
Cyclophilin 40 As A Novel Disaggregase, Jeremy Dustin Baker
USF Tampa Graduate Theses and Dissertations
The negative health and economic impacts of neurodegenerative diseases on Americans is astounding and accelerating with an aging population. The Alzheimer’s Association reports that 5.7 million Americans suffer from Alzheimer’s disease (AD), a number which is expected to increase to 14 million by 2050. In economic terms, AD and other neurodegenerative disorders will cost the US over $275 billion in 2018, rising to over $1 trillion annually by 2050. AD causes gross brain atrophy and is most damaging throughout the cortex and the hippocampus, regions required for higher cognitive function and memory. AD presents as tangles within neurons composed of …
Mass-Spectrometry Based Proteomics Of Age-Related Changes In Murine Microglia, Antwoine Flowers
Mass-Spectrometry Based Proteomics Of Age-Related Changes In Murine Microglia, Antwoine Flowers
USF Tampa Graduate Theses and Dissertations
The last century has seen a steady increase in the extension of the average lifespan. This has concomitantly produced higher incidences of age-related chronic degenerative diseases like Alzheimer’s and Parkinson’s diseases. Age is the single greatest risk factor for the development of not just these degenerative conditions but cancer as well. The aged niche undergoes a number of maladaptive changes that allow underlying conditions to present and progress. Exactly which changes, contribute to the progression of which disease is currently an area of intense study. However, these answers often present therapeutic targets for disease prevention. Age is characterized by a …
Regulation Of Palmitoylation Enzymes And Substrates By Intrinsically Disordered Regions, Krishna D. Reddy
Regulation Of Palmitoylation Enzymes And Substrates By Intrinsically Disordered Regions, Krishna D. Reddy
USF Tampa Graduate Theses and Dissertations
Protein palmitoylation refers to the process of adding a 16-carbon saturated fatty acid to the cysteine of a substrate protein, and this can in turn affect the substrate’s localization, stability, folding, and several other processes. This process is catalyzed by a family of 23 mammalian protein acyltransferases (PATs), a family of transmembrane enzymes that modify an estimated 10% of the proteome. At this point in time, no structure of a protein in this family has been solved, and therefore there is poor understanding about the regulation of the enzymes and their substrates. Most proteins, including palmitoylation enzymes and substrates, have …
Inhibiting The Interaction Between Grp94 And Myocilin To Treat Primary Open-Angle Glaucoma, Andrew Stothert
Inhibiting The Interaction Between Grp94 And Myocilin To Treat Primary Open-Angle Glaucoma, Andrew Stothert
USF Tampa Graduate Theses and Dissertations
Glaucoma is a neurodegenerative protein misfolding disorder classified by increases in IOP, damage to retinal ganglion cells (RGCs), optic nerve (ON) head damage, and progressive irreversible blindness. Primary open-angle glaucoma (POAG) is the most common form of glaucoma, constituting over 90% of clinical cases. POAG is observed in patients where normal outflow channels, mainly the trabecular meshwork (TM), are exposed at the angle formed by the iris and cornea. However, due to TM cellular dysfunction, aqueous outflow resistance is increased preventing normal circulation of aqueous humor. Recent studies have shown that in 2-4% of POAG cases, increased intracellular levels of …
Targeting Tau Degradation By Small Molecule Inhibitors For Treatment Of Tauopathies, Mackenzie Martin
Targeting Tau Degradation By Small Molecule Inhibitors For Treatment Of Tauopathies, Mackenzie Martin
USF Tampa Graduate Theses and Dissertations
Tauopathies are neurodegenerative diseases that affect millions of people around the world. Tauopathies include more than 20 neurodegenerative diseases. Some of the most common tauopathies are Alzheimer’s disease (AD), frontotemporal dementia (FTD), chronic traumatic encephalopathy (CTE), Pick’s disease, corticobasal degeneration, progressive supranuclear palsy (PSP), agyrophillic grain disease, and amyotrophic lateral sclerosis (ALS). These diseases can cause significant memory loss, behavioral changes, motor deficits and speech impairments. Tauopathies stem from accumulation of the microtubule associated protein tau (MAPT). Tau stabilizes microtubules and helps with axonal transport. In a disease state tau becomes hyperphosphorylated and truncated leading to its aggregation. More recently …
Cell Permeability Studies Of Aapeptides And Novel Molecular Probes For Ad, Ge Bai
Cell Permeability Studies Of Aapeptides And Novel Molecular Probes For Ad, Ge Bai
USF Tampa Graduate Theses and Dissertations
Alzheimer's diseases(AD) has been discovered and under research for more than 70 years, However there is no cure for these progressive and devastating diseases. Based on the following hypothsis: Aß metabolite problem/over production result in the accumulation, and lead to aggregation is the cause of Alzheimer’s disease. AApeptide and Melatonin derivatives can bind to Aß and block the aggregation of β amyloid monomers, decrease the toxicity of Aß to neurons and slow the progressive of Alzheimer’s diseases. In addition, AApeptide which mimic transmembrane peptide Tat will have similar transmembrane function. We have set up our goals as follows: 1) Using …
Strategies For Preventing Age And Neurodegenerative Disease-Associated Mitochondrial Dysfunction, Vedad Delic
Strategies For Preventing Age And Neurodegenerative Disease-Associated Mitochondrial Dysfunction, Vedad Delic
USF Tampa Graduate Theses and Dissertations
Mitochondrial dysfunction plays a pivotal role in the development of aging phenotypes and aging-associated neurodegenerative disorders, such as Alzheimer’s disease (AD), Parkinson’s disease (PD) and Amyotrophic lateral sclerosis (ALS). Strategies that restore mitochondrial dysfunction may rescue the deficits of central metabolism in these disorders and improve cell survival. For example, we found that modulating the mTOR signaling pathway in a tissue culture model of aging-induced mitochondrial DNA mutation enhanced mitochondrial function as evidenced by increased oxygen consumption. Our previous melatonin studies also led us to hypothesize that caloric restriction and the hormone melatonin would reverse brain mitochondrial dysfunction in animal …
Minocycline Treatment And The Necessity To Develop A Novel Outcome Measure For Children With Angelman Syndrome, Joseph Christopher Grieco
Minocycline Treatment And The Necessity To Develop A Novel Outcome Measure For Children With Angelman Syndrome, Joseph Christopher Grieco
USF Tampa Graduate Theses and Dissertations
Angelman syndrome (AS) is a rare genetic disorder affecting 1/10,000 to 1/20,000 births. This disorder arises through the genetic disruption of the maternal UBE3A allele, which when coupled with epigenetic silencing of the paternal allele UBE3A allele, gives rise to an absence of UBE3A protein in the central nervous system. Clinical manifestations of the syndrome vary in severity and include poor motor function, deficits in language and severe intellectual impairments. Previous research in the Angelman syndrome mouse model revealed abnormalities in dendritic spine density and morphology of hippocampal pyramidal cells. As seen in humans with AS, mice show abnormal behavioral …
Ube3a Role In Synaptic Plasticity And Neurodevelopmental Disorders.The Lessons From Angelman Syndrome., Irina Filonova
Ube3a Role In Synaptic Plasticity And Neurodevelopmental Disorders.The Lessons From Angelman Syndrome., Irina Filonova
USF Tampa Graduate Theses and Dissertations
Angelman Syndrome (AS) is a severe neurodevelopmental disorder that affects 1:12000 newborns. It is characterized by mental retardation, delayed major motor and cognitive milestones, seizures, absence of speech and excessive laughter. The majority of AS cases arise from deletions or mutations of UBE3A gene located on the chromosome 15q11-13. UBE3A codes for E3-ubiquitin ligase that target specific proteins for degradation. To date, a wide variety of Ube3a substrates has been identified. The accumulation of Ube3a-dependent proteins and their effect on the multitude of signal transduction pathways are` considered the main cause of the AS pathology. While the majority of research …
Proteolytic Processing Of The Amyloid Precursor Protein During Apoptosis And Cell Cycle: Implications For Alzheimer's Disease, Tina N. Fiorelli
Proteolytic Processing Of The Amyloid Precursor Protein During Apoptosis And Cell Cycle: Implications For Alzheimer's Disease, Tina N. Fiorelli
USF Tampa Graduate Theses and Dissertations
Alzheimer's disease is characterized by the presence of amyloid plaques, made up primarily of Aϐ peptides, and neurofibrillary tangles, containing hyperphosphorylated tau. Aϐ is generated by sequential proteolysis of the amyloid precursor protein (APP) by beta and gamma secretases. The leading hypothesis of Alzheimer's disease pathogenesis is the amyloid cascade hypothesis, which suggests that amyloid is central to the disease process. However, tau pathology correlates more closely with cognitive dysfunction and follows a predictable anatomical course through the brain. We hypothesize that if Aϐ is upstream of tau pathology and tau pathology follows this predictable course through the brain, Aϐ …
Multivariate Anti-Inflammatory Approaches To Rescue Neurogenesis And Cognitive Function In Aged Animals, Sandra Antonieta Acosta
Multivariate Anti-Inflammatory Approaches To Rescue Neurogenesis And Cognitive Function In Aged Animals, Sandra Antonieta Acosta
USF Tampa Graduate Theses and Dissertations
Studies have shown that there is a strong correlation between aging and neurodegenerative diseases. Aging is considered the number one risk factor to develop neuropathologies such as memory loss, senile dementia, Alzheimer's disease (AD), and Parkinson's disease. Neurodegenerative diseases tend to start during adulthood, and aggravate over time, making them difficult to prevent and to treat. In the Unites States, demographic studies by U.S. Bureau of the Census have determined that our aging population of >65 years is expected to increase from the present 35 million to 78 million in 2030. This would result, not only to an increase of …