Medicine and Health Sciences Commons^™

Bioinformatic Analysis Predicts Microglial Dysfunction In Murine Aging, Amadu Idrisa Jalloh

USF Tampa Graduate Theses and Dissertations

Age-related disease is a growing concern as the global geriatric population increases. Neurodegenerative diseases scale unfavorably in prevalence with aging and inflict disastrous consequences to human health and well-being. These disorders are challenging to investigate because they arise from complex molecular origins. The neuroimmune system is a common factor among these diseases and microglia play an important role in maintaining homeostasis in the central nervous system. Aging progressively impairs microglia by decreasing their ability to adapt and respond to noxious environmental stimuli or injury. Microglial dysfunction aggravates neurodegenerative pathology when microglia are unable to regulate neuroinflammation effectively. We investigated aging …

Immune Modulation As A Therapeutic Target In An Α-Synuclein Model Of Parkinson’S Disease, Meena Subhashini Subbarayan

USF Tampa Graduate Theses and Dissertations

Parkinson’s disease (PD) is the second most common neurodegenerative disorder affecting about 1.5 million people in the United States with more than 60,000 people diagnosed each year. It is classically characterized by four major symptoms: tremor, postural instability, stiffness in joints, and slow movement (bradykinesia). Pathologically PD is characterized by up to 70% loss of dopaminergic neurons in substantia nigra pars compacta (SNpc) of midbrain and accumulation of presynaptic protein called α-synuclein (α-syn) within dopaminergic neurons that extend to the striatum. This disrupts the nigrostriatal pathway leading to the motor symptoms seen in PD patients. Microglia, the innate immune cells …

Proteolysis Of Cx3cl1 Impacts Cx3cr1 Signaling And Therapeutic Benefits In A Tauopathy Model, Dylan John Finneran

USF Tampa Graduate Theses and Dissertations

Alzheimer’s disease (AD) is a progressive, neurodegenerative disorder and the most common form of dementia. The hallmark pathologies of AD are extracellular aggregates of amyloid-beta, intracellular aggregates of microtubule associated protein tau and increased neuroinflammation. Current therapeutics offer only symptomatic relief and clinical trials investigating therapeutic benefits of non-steroidal anti-inflammatory drugs have yielded no positive results. Therefore, recent work has focused on immunomodulators, such as CD200 and fractalkine, as potential therapeutic targets for AD.

Fractalkine (CX3CL1; FKN) is expressed as a transmembrane protein with an N-terminal chemokine domain followed by a long, mucin-like stalk. FKN can signal as a membrane-bound …

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 …

Implications Of Human Umbilical Cord Blood Cells: An Immunotherapeutic Strategy For Alzheimer's Disease, Donna Darlington

USF Tampa Graduate Theses and Dissertations

ABSTRACT

Alzheimer's disease (AD) is the most common progressive age related dementia and the fourth major cause of mortality in the elderly in the United States. AD is pathologically characterized by deposition of amyloid beta (Aβ) plaques in the brain parenchyma and neurofibrillary tangles (NFTs) within the neuronal soma. While pharmacological targets have been discovered, current strategies for the symptomatic or disease-modifying treatment of AD do not significantly slow or halt the underlying pathological progression of the disease. Consequently, more effective treatment is needed. One possibility for amelioration is using human umbilical cord blood cell (HUCBC) therapy. HUCBCs comprise a …