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Full-Text Articles in Life Sciences

Cyclophilin 40 As A Novel Disaggregase, Jeremy Dustin Baker Nov 2018

Cyclophilin 40 As A Novel Disaggregase, Jeremy Dustin Baker

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 ...


Interplay Between Mitochondrial Dysfunction And Epigenetic Alterations In Environmental Linked Parkinson's Disease, Adhithiya Charli Manohar Charle Jan 2018

Interplay Between Mitochondrial Dysfunction And Epigenetic Alterations In Environmental Linked Parkinson's Disease, Adhithiya Charli Manohar Charle

Graduate Theses and Dissertations

Parkinson's disease (PD) is a chronic age progressive neurodegenerative disease that affects about 1% of people over the age of 60. The hallmark pathological features of PD is characterized by the loss of 60-70% dopaminergic neurons, formation of Lewy bodies and aggregation of α-synuclein in the substantia nigra of the midbrain region. There are multiple factors that contribute to the origin of the disease and also these factors further trigger an avalanche of pathways, thus prominently increasing the risk of incurring PD. Although the etiopathology of PD is not very well understood, growing evidences on mitochondrial dysfunction and oxidative ...


Characterization Of A Murine Model Of Mucopolysaccharidosis Type Iiid: A Knockout Model, Maryam Jamil Jan 2016

Characterization Of A Murine Model Of Mucopolysaccharidosis Type Iiid: A Knockout Model, Maryam Jamil

Graduate Theses and Dissertations

The Mucopolysaccharidoses (MPS) are a class of lysosomal storage disorders, characterized by the primary lysosomal storage of either single or multiple species of glycosaminoglycan (GAG) which leads to cell, tissue, and organ dysfunction. This is manifested clinically by either bone/connective tissue disease, central nervous system (CNS) disease, or both, and often results in premature death. Mucopolysaccharidosis type III is a heterogeneous neuropathological disorder characterized by an accumulation of the heparan sulfate (HS). Of the four known types of MPS III in humans (A (OMIM: 252900), B (252920), C (252930), D (252940)), all have murine models except IIID. Additional to ...


The Inflammatory Response Initiated By The Spleen To Ischemic Stroke, Hilary Seifert Jan 2013

The Inflammatory Response Initiated By The Spleen To Ischemic Stroke, Hilary Seifert

Graduate Theses and Dissertations

The peripheral immune system plays a role in delayed neural injury after stroke. This response originates from the spleen as splenectomy prior to middle cerebral artery occlusion (MCAO) in rats significantly reduces infarct volume in the brain. This research is based on the hypothesis that inhibiting the splenic response will reduce neurodegeneration after stroke. Studies in animals have implicated lymphocytes as the immune cell type that is detrimental following MCAO. Interferon gamma (IFNγ) has been identified as a pro-inflammatory cytokine that is also detrimental following stroke. IFNγ is important because it activates microglia and macrophages in a pro-inflammatory nature that ...


Roles Of Manganese And Protein Kinase Signaling In Cell Culture And Animal Models Of Prion Disease, Dustin Paul Martin Jan 2013

Roles Of Manganese And Protein Kinase Signaling In Cell Culture And Animal Models Of Prion Disease, Dustin Paul Martin

Graduate Theses and Dissertations

Despite several decades of dedicated research by a diverse array of researchers from around the globe, the molecular mechanisms underlying neuronal loss during transmissible spongiform encephalopathy (TSE) remain to be elucidated. Additionally, the etiology of so-called "sporadic" cases of TSE, which represents the vast majority of cases in both humans and animals, remains unknown. Several recent advancements in the understanding of other protein misfolding neurodegenerative disorders including Alzheimer's Disease (AD), Parkinson's Disease (PD), Amyotrophic Lateral Sclerosi (ALS), and TSE have highlighted the similarities between disease etiopathogenesis which may broaden the diversity of potential future therapies. As our understanding ...


Proteolytic Processing Of The Amyloid Precursor Protein During Apoptosis And Cell Cycle: Implications For Alzheimer's Disease, Tina N. Fiorelli Jan 2013

Proteolytic Processing Of The Amyloid Precursor Protein During Apoptosis And Cell Cycle: Implications For Alzheimer's Disease, Tina N. Fiorelli

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 ...


Transcriptional Regulation Of Proapoptotic Kinase Pkcî´ Expression In Dopaminergic Neurons: Relevance To Gene-Gene And Gene-Environment Interactions In Neurodegeneration, Huajun Jin Jan 2010

Transcriptional Regulation Of Proapoptotic Kinase Pkcî´ Expression In Dopaminergic Neurons: Relevance To Gene-Gene And Gene-Environment Interactions In Neurodegeneration, Huajun Jin

Graduate Theses and Dissertations

We investigated the mechanisms of transcriptional regulation of the PKCδ gene. By deletion analysis of the ~1.4 kb (-1448 to +1, relative to transcription start site) 5'-flanking sequence of the mouse PKCδ gene, we have identified a basal promoter region, nucleotide -148 to +1, required for sufficient PKCδ transcription in NIE115, MN9D, and N2a cells. We further identified two NFκB binding sites (κB 1, κB 2) as well as a NERF1a site within the basal promoter as key regulatory elements in the mouse PKCδ TATA-less promoter. Subsequent functional studies using site-directed mutation analysis revealed that κB 1, but ...