Medicine and Health Sciences Commons^™

Involvement Of The Renin Angiotensin System In Marfan Syndrome Associated Thoracic Aortic Aneurysms, Jeff Zheying Chen

Theses and Dissertations--Physiology

Thoracic aortic aneurysms (TAAs) are clinically-silent dilations of the aorta which greatly increase the risk of aortic rupture, a condition with 50-90% mortality. Marfan syndrome (MFS) is caused by mutations in fibrillin-1 (FBN1) and is associated with TAAs. Due to an absence of validated and effective pharmacologic therapies to prevent or reverse TAA, most MFS patients require surgical aortic repair. Understanding MFS associated TAA pathogenesis would direct development of new pharmacologic therapies. Previous research has implicated the renin angiotensin system in TAA. In both males and females, angiotensinogen (AGT) is cleaved serially to generate the main effector peptide angiotensin II …

Ceramide-Enriched Extracellular Vesicles: A Role In Enhancing Amyloid-Beta Neurotoxicity And Mitochondrial Damage In Alzheimer’S Disease, Ahmed Elsherbini

Theses and Dissertations--Physiology

Alzheimer’s disease (AD) is an age-dependent, progressive, neurodegenerative disorder that is characterized clinically by the impairment of cognitive functions concomitant with behavioral and personality changes. AD is associated with distinct pathological hallmarks, namely, intracellular neurofibrillary tangles comprised of hyperphosphorylated tau protein, extracellular amyloid beta (Aβ) plaques, and marked brain atrophy. Besides their main role as the core component of amyloid plaques, oligomeric Aβ have been shown to be neurotoxic. The exact mechanism of Aβ neurotoxicity is yet to be elucidated.

Recently, a pathogenic function of small extracellular vesicles- also known as exosomes- has been proposed, suggesting that exosomes can transfer …

Apoe As A Metabolic Regulator In Humans, Mice, And Astrocytes, Brandon C. Farmer

Theses and Dissertations--Physiology

Altered metabolic pathways appear to play central roles in the pathophysiology of late-onset Alzheimer’s disease (AD). Carrier status of the E4 allele of the APOE gene is the strongest genetic risk factor for late-onset AD, and increasing evidence suggests that E4 carriers may be at an increased risk for neurodegeneration based on inherent metabolic impairments. A new appreciation is forming for the role of APOE in cerebral metabolism, and how nutritional factors may impact this role. In chapter 1, the literature on nutritional interventions in E4 carriers aimed at mitigating disease risk is reviewed. Studies investigating the mechanism by which …